Relaxation Responses (relaxation + response)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


The Effect of Korean Red Ginseng Extract on the Relaxation Response in Isolated Rabbit Vaginal Tissue and Its Mechanism

THE JOURNAL OF SEXUAL MEDICINE, Issue 9 2008
Sun-Ouck Kim MD
ABSTRACT Introduction., Ginseng is an herbal medicine with a variety of biological activities. Aim., The purpose of this study was to investigate the effect of Korean red ginseng (KRG) extract on the relaxation response in isolated rabbit vaginal tissue and its mechanism as a potential therapeutic agent for female sexual dysfunction. Method., Strips of rabbit vagina were mounted in organ chambers to measure isometric tension. After the strips were precontracted with phenylephrine, the contractile responses to KRG extract (1,20 mg/mL), nitric oxide inhibitor (N[omega]-nitro-L-arginine methyl ester [L-NAME]), an inhibitor of soluble guanylate cyclase (methylene blue), an inhibitor of Ca2+ -activated K+ channels (tetraethylammonium [TEA]), and an adenosine triphosphate (ATP)-sensitive K+ channel blocker (glybenclamide) were examined. Main Outcome Measures., The relaxation of the vaginal tissue strip was assessed after treating KRG extract or other chemicals. Results., KRG (1,20 mg/mL) extract relaxed the vaginal tissue strip in a dose-dependent manner up to 85%. The relaxation effect was significantly inhibited by L-NAME (30 µM) and methylene blue (30 µM) (P < 0.05). In addition, KRG inhibited the contraction induced by depolarization with 10, 20, and 40 mM KCl. The KRG-induced relaxation effect was significantly inhibited by TEA (300 µM) (P < 0.05), and not by glybenclamide (30 µM). Conclusions., These data show that KRG extract has a relaxing effect on rabbit vaginal smooth muscle tissue. These effects might be mediated partly through the NO pathway and hyperpolarization via Ca2+ -activated K+ channels. Kim S-O, Kim MK, Lee H-S, Park JK, and Park K. The effect of Korean red ginseng extract on the relaxation response in isolated rabbit vaginal tissue and its mechanism. J Sex Med 2008;5:2079,2084. [source]


Hydrogen,potassium ATPase inhibitors induce relaxation on rabbit prostatic strips in vitro

INTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2002
Ihsan Bagcivan
Summary Background : To determine the relaxant effect of omeprazole and lansaprazole, hydrogen,potassium (H+,K+) ATPase inhibitors, on rabbit prostatic tissue in vitro. Methods : Male New Zealand white rabbits were sacrificed and their prostatic tissues were removed. The prostatic stromal strips were mounted in organ baths and relaxation responses were obtained in precontracted tissues with phenylephrine, carbachol and potassium chloride (KCl). Relaxation responses were controlled in the presence of various antagonists to explain the mechanism for relaxation exerted by omeprazole and lansaprazole. Results : Omeprazole and lansaprazole caused similar relaxation responses in the prostatic strips precontracted with phenylephrine, carbachol and KCl. The addition of prostaglandin synthase inhibitor indomethacin, nitric oxide synthase inhibitor L-NAME, potassium channel blockers, glibenclamide and tetraethylammonium into the organ baths did not change the relaxations induced by omeprazole and lansaprazole in vitro. Conclusion : Omeprazole and lansaprazole cause a relaxation in prostatic stromal tissue precontracted with phenyephrine, carbachol and KC1 in vitro. This relaxant effect is independent of H+,K+ ATPase inhibition. Additionally, cyclooxygenase and nitric oxide pathways do not contribute to this relaxant effect. Further studies are required to determine whether these drugs may have a beneficial effect in the non-operative treatment of benign prostatic hyperplasia. [source]


Comparison of relaxation responses to multiple vasodilators in TxA2 -analog and endothelin-1-precontracted pulmonary arteries

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2007
C. Piamsomboon
Background:, Peri-operative pulmonary hypertension can lead to right ventricular dysfunction and to an increase in morbidity and mortality. Altered function of the pulmonary vascular endothelium and vasoconstriction play a crucial role in the development of elevated pulmonary vascular resistance. Because pulmonary artery vasoreactivity is dependent on many factors including the constricting agent that precipitated the event therefore the aim of the current study was to investigate the effectiveness of different classes of vasodilator agents to reverse endothelin-1 (ET-1) or thromboxane A2 (TxA2)-induced vasoconstriction in porcine pulmonary artery (PA) in vitro. Methods:, Relaxation responses to vasodilatory drugs were studied in PA precontracted with ET-1 (1 × 10,8 M) or TxA2 analog (U46619, 1 × 10,8 M). All vasodilating drugs were added in a cumulative fashion and isometric tension measurements were obtained using an organ chamber technique. Results:, In both groups relaxation responses to the vasodilators were dose dependent. When ET-1 was used as a constrictor nitroglycerin and milrinone caused nearly complete (80,100%) relaxation, whereas other agents were of limited effectiveness (40,50%). On the other hand, in the vessels constricted with U46619, olprinone, indomethacin, prostaglandin E1 (PGE1), nitroglycerin, milrinone and clevidipine induced complete (90,110%) vasodilatation but brain natriuretic peptide (BNP), l -arginine, and isoproterenol relaxed the vessels maximally by 45,60%. Conclusions:, Nitroglycerin and milrinone are very effective in reversing ET-1 and U46619-induced pulmonary vasoconstriction in vitro. The effectiveness of other drugs studied was dependent on the type of constrictor used. BNP, l -arginine and isoproterenol were shown to have minimal vasodilatory effects in porcine PA. [source]


The Effect of Ovariectomy on Rat Vaginal Tissue Contractility and Histomorphology

THE JOURNAL OF SEXUAL MEDICINE, Issue 2 2006
F. Fatih Önol MD
ABSTRACT Introduction., Ovarian hormones have an important role in age-related genital arousal disorders; however, our knowledge regarding possible vaginal wall morphology and contractility changes in low-hormonal states is limited. Aims., To investigate morphological and functional alterations in the vaginal tissue in a rat ovariectomy model and to show the differences between proximal and distal vagina. Methods., Six weeks following ovariectomy, vaginal tissues were examined under light and electron microscopy. Circularly cut distal and proximal tissues were studied in the organ bath under isometric tension and compared with age-matched controls. Contractile responses to electrical field stimulation (EFS), phenylephrine, carbachol, and the effects of alpha-1 and alpha-2 blockade on EFS-induced contractility were investigated. Relaxation responses to EFS and vardenafil were investigated in precontracted strips. Main Outcome Measures., Differences between control and ovariectomy groups in terms of vaginal tissue contractility and histomorphological properties. Results., Distal vagina showed different epithelial characteristics and a better-developed muscularis compared with proximal vagina. Ovariectomy caused thinning of the epithelium, severe degeneration in epithelial architecture, and smooth muscle atrophy. Contraction and relaxation responses of distal strips were significantly lower in ovariectomized rats. Contractile responses to neuropharmacological stimulation were insignificant in proximal strips of both groups. EFS-induced contractions in distal strips diminished significantly after alpha-1 and alpha-2 adrenergic blockade. EFS caused frequency-dependent relaxation responses in precontracted distal strips, which were significantly decreased after nitric oxide synthase inhibition. Conclusions., Ovariectomy causes significant alteration in rat vaginal tissue morphology and contractility. Contraction and relaxation responses of distal vagina are significantly greater compared with morphologically distinct proximal vagina. Alpha-1 and alpha-2 receptors are the main mediators of contraction in distal rat vaginal tissue whereas nitric oxide pathway may have at least a partial role in relaxation. Main mediators of the rat vaginal tissue relaxation and the effect of ovariectomy on this regulation are yet to be defined. Önol FF, Ercan F, and Tarcan T. The effect of ovariectomy on rat vaginal tissue contractility and histomorphology. J Sex Med 2006;3:233,241. [source]


Insurmountable antagonism of AT-1015, a 5-HT2 antagonist, on serotonin-induced endothelium-dependent relaxation in porcine coronary artery

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2003
Mamunur Rashid
The purpose of this study was to examine the inhibitory effects of AT-1015, a newly synthesized 5-HT2 receptor antagonist, on serotonin-induced endothelium-dependent relaxation in U 46619 (5 times 10,9m)-precontracted porcine coronary artery pre-incubated with ketanserin (3 times 10,6m), and then compare its effects with another potent 5-HT2 antagonist, ritanserin. The investigation showed that AT-1015 (10,8,10,6m) caused rightward shift with significant inhibition of maximum relaxation response induced by serotonin in porcine coronary artery with endothelium. Ritanserin caused a rightward shift of serotonin-induced relaxation without decreasing maximum response at 10,9 and 10,8m, but it inhibited the maximum relaxation response at 10,7m. The study showed that AT-1015 and ritanserin had no inhibitory effect on bradykinin-induced relaxation in porcine coronary artery with endothelium. Thus, these findings suggested that AT-1015 at concentrations of 10,8,10,6m caused noncompetitive blockade of serotonin-induced endothelium-dependent relaxation in porcine coronary artery. The antagonistic effects of AT-1015 on serotonin-induced relaxation were different from that of ritanserin, except at 10,7m ritanserin. The variation of inhibitory effects between these two 5-HT2 antagonists may be due to the different chemical structure and/or interaction sites at the receptor. [source]


PREDICTING SENSORY COHESIVENESS, HARDNESS AND SPRINGINESS OF SOLID FOODS FROM INSTRUMENTAL MEASUREMENTS

JOURNAL OF TEXTURE STUDIES, Issue 2 2008
R. DI MONACO
ABSTRACT The sensory evaluation of cohesiveness, hardness and springiness of 15 solid food samples was performed by eight trained assessors. The rheologic response of the 15 samples was estimated by performing cyclic compression tests and stress,relaxation tests. From the force,deformation curves of the first two cycles of the compression test, texture profile analysis parameters related to cohesiveness, hardness and springiness were calculated. Young's modulus (E), strain (di) and stress (si) at peak as well as irrecoverable strain (ri) and irrecoverable work (Li) were monitored during the first five cycles. From the stress,relaxation response, Peleg's linearization model parameters, K1 and K2, were estimated by best-fit regression. These parameters were used for predicting sensory attributes. Hardness and springiness were both accurately predicted by rheologic properties, while cohesiveness prediction was less representative. PRACTICAL APPLICATIONS This study contributes to enhance the knowledge in the research area of sensory instrumental correlation. Also, the research allows to better understanding that no single instrument is able to measure all texture attributes adequately. In fact, the results demonstrate that both stress,relaxation and cyclic compression tests need to be performed for the correct prediction of sensory responses. [source]


The Effect of Korean Red Ginseng Extract on the Relaxation Response in Isolated Rabbit Vaginal Tissue and Its Mechanism

THE JOURNAL OF SEXUAL MEDICINE, Issue 9 2008
Sun-Ouck Kim MD
ABSTRACT Introduction., Ginseng is an herbal medicine with a variety of biological activities. Aim., The purpose of this study was to investigate the effect of Korean red ginseng (KRG) extract on the relaxation response in isolated rabbit vaginal tissue and its mechanism as a potential therapeutic agent for female sexual dysfunction. Method., Strips of rabbit vagina were mounted in organ chambers to measure isometric tension. After the strips were precontracted with phenylephrine, the contractile responses to KRG extract (1,20 mg/mL), nitric oxide inhibitor (N[omega]-nitro-L-arginine methyl ester [L-NAME]), an inhibitor of soluble guanylate cyclase (methylene blue), an inhibitor of Ca2+ -activated K+ channels (tetraethylammonium [TEA]), and an adenosine triphosphate (ATP)-sensitive K+ channel blocker (glybenclamide) were examined. Main Outcome Measures., The relaxation of the vaginal tissue strip was assessed after treating KRG extract or other chemicals. Results., KRG (1,20 mg/mL) extract relaxed the vaginal tissue strip in a dose-dependent manner up to 85%. The relaxation effect was significantly inhibited by L-NAME (30 µM) and methylene blue (30 µM) (P < 0.05). In addition, KRG inhibited the contraction induced by depolarization with 10, 20, and 40 mM KCl. The KRG-induced relaxation effect was significantly inhibited by TEA (300 µM) (P < 0.05), and not by glybenclamide (30 µM). Conclusions., These data show that KRG extract has a relaxing effect on rabbit vaginal smooth muscle tissue. These effects might be mediated partly through the NO pathway and hyperpolarization via Ca2+ -activated K+ channels. Kim S-O, Kim MK, Lee H-S, Park JK, and Park K. The effect of Korean red ginseng extract on the relaxation response in isolated rabbit vaginal tissue and its mechanism. J Sex Med 2008;5:2079,2084. [source]


The relative importance of the time-course of receptor occupancy and response decay on apparent antagonist potency in dynamic assays

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2000
M. Corsi
1 The potency of the ,1 -adrenoceptor antagonist atenolol was measured as an inhibitor of responses to isoprenaline in guinea-pig left atria. Measurements were made in two ways, firstly, by pre-incubating the atria with a given concentration of atenolol followed by an isoprenaline dose,response curve and, secondly, by measuring the response to isoprenaline followed by addition of atenolol. 2 It was found that the estimation of atenolol potency as an antagonist of ,1 -adrenoceptors by these two methods gave divergent results. Specifically, it was found that the isoprenaline-induced increased rate of myocardial relaxation was resistant to receptor blockade. Thus, the rate-limiting step in the relaxation response was dissociated from receptor activation and therefore, could not be used for the measurement of receptor occupancy. 3 In contrast, the positive inotropic response was very responsive to receptor occupancy. However, when atenolol was used to block a steady-state isoprenaline response, there was a complicating depression of basal inotropy after receptor blockade that obfuscated measurement of receptor blockade. 4 In general, these data indicated that the blockade of a steady-state agonist response to measure the potency of an antagonist might in some cases yield erroneous results. These studies indicate some caution in the interpretation of blockade responses in pre-contracted or pre-stimulated pharmacological preparations. [source]


Chronic inhibition of nitric-oxide synthase induces hypertension and erectile dysfunction in the rat that is not reversed by sildenafil

BJU INTERNATIONAL, Issue 1 2010
Serap Gur
Study Type , Aetiology (case control) Level of Evidence 3b OBJECTIVE To evaluate the effect of N(G)-nitro- l -arginine methyl ester (L-NAME)-induced hypertension (HT) on erectile function in the rat and determine if the phosphodiesterase (PDE)-5 inhibitor, sildenafil, can reverse the effects of nitric oxide (NO) deficiency, as HT is a risk factor for erectile dysfunction (ED) and the NO synthase (NOS) inhibitor L-NAME induces NO-deficient HT. MATERIALS AND METHODS Thirty-six adult Sprague-Dawley male rats were divided into three groups, i.e. a control, L-NAME-HT (40 mg/rat/day in the drinking water for 4 weeks), and sildenafil-treated L-NAME-HT (1.5 mg/rat/day sildenafil, by oral gavage concomitantly with L-NAME). The erectile response expressed as a ratio of intracavernosal pressure (ICP)/mean arterial pressure (MAP), evaluated after electrical stimulation of the right cavernous nerve. The isometric tension of corpus cavernosum smooth muscle (CCSM) was measured in organ-bath experiments. NOS expression was determined immunohistochemically for neuronal (n)NOS and by Western blot analysis for endothelial (e) and inducible (i) NOS protein. cGMP levels were evaluated by enzyme-linked immunosorbent assay. RESULTS The erectile response was diminished in the HT group. Nitrergic and endothelium-dependent relaxation was reduced, while the relaxation response to sodium nitroprusside and contractile response to phenylephrine were not altered in CCSM from L-NAME-treated rats. HT rats showed decreased expression of nNOS, whereas eNOS and iNOS protein expression was increased. Sildenafil partly restored endothelial and molecular changes in CCSM from HT rats, but did not reverse the decreased erectile response, even as cGMP levels returned to normal levels. CONCLUSIONS Sildenafil treatment did not correct the ED in L-NAME-treated HT rats. Under sustained high blood pressure, up-regulation of PDE5 expression failed to reverse the depletion of neuronal NO and/or impaired nNOS activity. However, endothelium-dependent relaxation was restored. Drug targeting of neuronal dysfunction might delay the onset of ED in HT. [source]


GINKGO BILOBA EXTRACT CAUSES DECREASE IN HEART RATE IN AGED SPONTANEOUSLY HYPERTENSIVE RATS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2007
Y Kubota
SUMMARY 1We previously reported that Ginkgo biloba extract (GBE) improves cardiovascular function in young spontaneously hypertensive rats (SHR). In the present study, changes in the cardiovascular parameters of aged SHR were examined following a 4-week diet of GBE. 2Feeding with GBE significantly decreased the heart rate and blood flow velocity in the tails of aged SHR. The contractile and relaxation responses were unchanged in isolated aortas and mesenteric arteries of aged SHR fed the GBE diet. The GBE diet did not influence the protein levels of endothelial nitric oxide synthase or soluble guanylyl cyclase in the aortas. 3These findings indicate that in aged SHR, the ingestion of GBE may cause bradycardia without a beneficial effect on the vascular relaxation response. Intake of GBE as a supplement in elderly hypertensive patients should be carefully monitored. [source]


Abstract no.: 6 Endothelium-dependent relaxation by purinergic receptors in the aorta of apolipoprotein E-deficient mice

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2005
A. Korda
Previously we reported that the acetylcholine-induced relaxation in the isolated aorta of apolipoprotein E-deficient (apoE -/- ) mice deteriorates after the development of atherosclerotic plaques, but remains normal in adjacent, plaque-free segments. The present study investigated the presence of functional purinergic receptors in the murine aorta, and whether their function changes before or after the development of atherosclerosis. Endothelium-dependent relaxation was measured in aorta segments of apoE -/- , C57BL6 (WT) and human apoAI-overexpressing apoE -/- mice (apoAI/apoE -/- ) on regular chow. Rings were isometrically contracted with phenylephrine to 50% of their maximum force before performing cumulative concentration-response curves to different nucleotides or their stable analogues. After the functional study, the cross-sectional area of the plaque was determined in every segment. The nucleotides induced complete (UTP, UDP, ATP) or partial (ADP) relaxation that was abolished by endothelial cell removal or nitric oxide (NO) synthase inhibition. The responses pointed to the presence of functional P2y1, P2y2 or P2y4 receptors on endothelial cells. RT-PCR confirmed the presence of P2y1 and P2y4 mRNA in the aorta of WT mice. Nucleotide responses were unaltered in lesion-free apoE -/- mice (5 months). However, in atherosclerotic segments of apoE -/- mice (18 months), the relaxation to ATP was impaired compared to age-matched WT controls (maximum amplitude (Emax) 25 ± 14%, n = 6 vs. 90 ± 3%, n = 5, P < 0.01). A similar defect was seen for the stable analogue ATP-gamma-S (Emax 36 ± 12% vs. 86 ± 3%, P < 0.01). Atherosclerotic apoE -/- segments were less sensitive to the NO donor spermineNONOate (pD2 6.74 ± 0.18) than WT segments (7.25 ± 0.20), but maximum relaxation was unaltered. In non-atherosclerotic aorta segments of the same apoE -/- mice all relaxation responses remained normal and were not different from WT. Strong negative correlations (P < 0.001) existed between lesion size and the Emax for ATP (rs = ,0.82) and ATP-gamma-S (rs = ,0.73) in apoE -/- mice. ApoAI overexpression improved the purinergic responses (Emax ATP 64 ± 9%, ATP-gamma-S 64 ± 10%, n = 5) and these were not different from WT (P > 0.05). An analysis of covariance with plaque size as covariate suggested that this benefit was secondary to the strongly reduced plaque formation in apoAI/apoE -/- mice. It is concluded that functional P2 y receptors are present on murine aortic endothelium. Furthermore, endothelium-dependent purinergic relaxation declines after plaque development. This deterioration involves decreased bioavailability of NO rather than enhanced ATP degradation. The defect is, however, not systemic since the responses remain unaltered in plaque-free segments of atherosclerosis-prone apoE -/- mice. [source]


Effect of hypothyroidism on the nitrergic relaxant responses of corpus cavernosal smooth muscle in rabbits

INTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2006
BULENT SARAC
Background:, The incidence of hormonal dysfunction as a cause of impotence remains controversial. However, several recent studies have reported evidence of hormonal abnormalities in 25,35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. Methods:, In the present study, we examined nitrergic responses in hypothyroidism in rabbit corpus cavernosum and compared them with controls. Results:, Carbachol-induced relaxation responses and electrical field stimulation (EFS)-induced frequency-dependent relaxations decreased significantly in hypothyroid rabbits. Papaverine and sodium nitroprusside (SNP)-induced relaxation responses did not change significantly in hypothyroid rabbits. The contraction responses of phenylephrine and EFS-induced frequency-dependent contractions were significantly decreased in the hypothyroid group. Conclusions:, We can speculate that the reduction of relaxant responses to EFS and carbachol in hypothyroid rabbits can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium or a reduction of muscarinic receptor density. Also, decreases in contraction responses may depend on diminished adrenoceptor density. [source]


Hydrogen,potassium ATPase inhibitors induce relaxation on rabbit prostatic strips in vitro

INTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2002
Ihsan Bagcivan
Summary Background : To determine the relaxant effect of omeprazole and lansaprazole, hydrogen,potassium (H+,K+) ATPase inhibitors, on rabbit prostatic tissue in vitro. Methods : Male New Zealand white rabbits were sacrificed and their prostatic tissues were removed. The prostatic stromal strips were mounted in organ baths and relaxation responses were obtained in precontracted tissues with phenylephrine, carbachol and potassium chloride (KCl). Relaxation responses were controlled in the presence of various antagonists to explain the mechanism for relaxation exerted by omeprazole and lansaprazole. Results : Omeprazole and lansaprazole caused similar relaxation responses in the prostatic strips precontracted with phenylephrine, carbachol and KCl. The addition of prostaglandin synthase inhibitor indomethacin, nitric oxide synthase inhibitor L-NAME, potassium channel blockers, glibenclamide and tetraethylammonium into the organ baths did not change the relaxations induced by omeprazole and lansaprazole in vitro. Conclusion : Omeprazole and lansaprazole cause a relaxation in prostatic stromal tissue precontracted with phenyephrine, carbachol and KC1 in vitro. This relaxant effect is independent of H+,K+ ATPase inhibition. Additionally, cyclooxygenase and nitric oxide pathways do not contribute to this relaxant effect. Further studies are required to determine whether these drugs may have a beneficial effect in the non-operative treatment of benign prostatic hyperplasia. [source]


Effect of ropivacaine on endothelium-dependent phenylephrine-induced contraction in guinea pig aorta

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2007
P. L. Lin
Background:, Previous studies have shown that ropivacaine has biphasic vascular effects, causing vasoconstriction at low concentrations and vasorelaxation at high concentrations. This study was designed to examine the role of the endothelium during accidental intravascular absorption of ropivacaine, and to elucidate the mechanisms responsible. Methods:, Isolated guinea pig aortic rings were suspended for isometric tension recording. The effects of ropivacaine on endothelium-intact and endothelium-denuded aortic rings were assessed. Endothelium-intact aortic rings were pre-contracted with phenylephrine before being exposed to ropivacaine and acetylcholine, in order to generate and compare concentration,response curves. In the absence and presence of yohimbine, propranolol, atropine, indometacin, NG -nitro- l -arginine methyl ester (l -NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or methylene blue, the contractile response induced by ropivacaine was assessed on endothelium-intact aortic rings pre-contracted with phenylephrine. Results:, Ropivacaine (3 × 10,4 to 10,2 mol/l) produced vasoconstriction in endothelium-denuded aortic rings, whereas no such response was observed in aortic rings with intact endothelium. In phenylephrine pre-contracted intact aortic rings, ropivacaine induced a greater degree of vasorelaxation than did acetylcholine. Yohimbine, propranolol and atropine all failed to affect the relaxation responses induced by ropivacaine. However, pre-treatment with indometacin (cyclo-oxygenase inhibitor), l -NAME (nitric oxide synthase inhibitor), methylene blue (soluble guanylyl cyclase inhibitor) or ODQ (soluble guanylyl cyclase inhibitor), significantly decreased the ropivacaine-induced relaxation of endothelium-intact aortic rings (3 × 10,4 to 10,2 mol/l). Conclusions:, Ropivacaine elicits an endothelium-dependent vasorelaxation in phenylephrine pre-contracted aortic rings via the nitric oxide,cyclic guanosine 3,,5,-monophosphate pathway and the prostaglandin system. [source]


Comparison of relaxation responses to multiple vasodilators in TxA2 -analog and endothelin-1-precontracted pulmonary arteries

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2007
C. Piamsomboon
Background:, Peri-operative pulmonary hypertension can lead to right ventricular dysfunction and to an increase in morbidity and mortality. Altered function of the pulmonary vascular endothelium and vasoconstriction play a crucial role in the development of elevated pulmonary vascular resistance. Because pulmonary artery vasoreactivity is dependent on many factors including the constricting agent that precipitated the event therefore the aim of the current study was to investigate the effectiveness of different classes of vasodilator agents to reverse endothelin-1 (ET-1) or thromboxane A2 (TxA2)-induced vasoconstriction in porcine pulmonary artery (PA) in vitro. Methods:, Relaxation responses to vasodilatory drugs were studied in PA precontracted with ET-1 (1 × 10,8 M) or TxA2 analog (U46619, 1 × 10,8 M). All vasodilating drugs were added in a cumulative fashion and isometric tension measurements were obtained using an organ chamber technique. Results:, In both groups relaxation responses to the vasodilators were dose dependent. When ET-1 was used as a constrictor nitroglycerin and milrinone caused nearly complete (80,100%) relaxation, whereas other agents were of limited effectiveness (40,50%). On the other hand, in the vessels constricted with U46619, olprinone, indomethacin, prostaglandin E1 (PGE1), nitroglycerin, milrinone and clevidipine induced complete (90,110%) vasodilatation but brain natriuretic peptide (BNP), l -arginine, and isoproterenol relaxed the vessels maximally by 45,60%. Conclusions:, Nitroglycerin and milrinone are very effective in reversing ET-1 and U46619-induced pulmonary vasoconstriction in vitro. The effectiveness of other drugs studied was dependent on the type of constrictor used. BNP, l -arginine and isoproterenol were shown to have minimal vasodilatory effects in porcine PA. [source]


COMPARISON OF MECHANICAL TESTS FOR EVALUATING TEXTURAL CHANGES IN POTATOES DURING THERMAL SOFTENING

JOURNAL OF TEXTURE STUDIES, Issue 6 2002
W. K. SOLOMON
ABSTRACT The changes in the texture of cylindrical samples of potato tissues immersed in water at 60, 70, 80 and 90C for up to 80 min were monitored at each temperature in terms of tangent modulus of elasticity in axial and radial compression tests, and elasticity and viscosity parameters in creep and stress relaxation tests. The magnitude of all mechanical test parameters decreased with an increase in heating time and temperature. The creep and stress relaxation responses of individual potato samples were adequately represented by respective mechanical models (R2= 0.94 to 0.99). The mechanical test parameters followed apparent first-order degradation kinetics due to the effect of thermal softening, and the rate constant was used as an index of the sensitivity of a mechanical test. The radial compression test was relatively more sensitive than the axial test. Based on an overall comparison, the parameters from creep and stress relaxation tests were found to be the most sensitive in describing the textural changes during thermal softening of potatoes. [source]


Lower oesophageal sphincter relaxation evoked by stimulation of the dorsal motor nucleus of the vagus in ferrets

NEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2002
T. P. Abrahams
Abstract, An understanding of the neural control of lower oesophageal sphincter (LOS) relaxation is clinically relevant because transient LOS relaxations (TLOSRs) are a mechanism of acid reflux into the oesophagus. Preganglionic motor neurones innervating the LOS are localized in the dorsal motor nucleus of the vagus (DMV). Based on a single study in cats, it is now widely accepted that these neurones are functionally organized into two separate populations, such that stimulation of the caudal and rostral DMV evokes LOS relaxation and contraction, respectively. Our goal was to map the functional LOS responses to chemical stimulation in the DMV and nucleus tractus solitarius (NTS) of ferrets, an animal model commonly used for conscious studies on TLOSRs, and to test whether DMV-evoked LOS relaxation is mediated through hexamethonium-sensitive vagal-inhibitory pathways to the LOS. We used miniaturized manometry with Dentsleeve to monitor LOS and oesophageal pressures in decerebrate unanaesthetized ferrets. LOS relaxation was evoked readily in response to gastric insufflation, which shows that the vago,vagal reflex was intact in this preparation. Microinjections of l -glutamate (12.5 nmol L,1in 25 nL) were made into the DMV from approximately ,,1.5 to +,2.0 mm relative to the obex. Microinjections into the caudal (, 1.5 to +,0.0 mm behind obex) and intermediate (+ 0.1 to +,1.0 mm rostral to obex) DMV both significantly decreased LOS pressure, and complete LOS relaxation was noted in 28/32 and 11/18 cases, respectively. LOS relaxation responses to DMV microinjection were highly reproducible and abolished by bilateral vagotomy or hexamethonium (15 mg kg,1intravenously). A nitric oxide synthase inhibitor (l -NAME 100 mg kg,1intramuscularly) significantly increased the time taken to reach the maximal response. Increases in LOS pressure (24 ± 4 mmHg; n = 3) were obtained only when stimulation sites were located equal to greater than 1.5 mm rostral to the obex. LOS relaxation (, 78 ± 10%; n = 6) was evoked by stimulation of the NTS but not immediately outside of the NTS (11 ± 27%; n = 5). We conclude that there is a very extensive population of ,inhibitory' motor neurones in the DMV that may account for the predominant vagal-inhibitory tone in ferrets. As NTS stimulation evokes LOS relaxation and the predominant response to DMV stimulation is also LOS relaxation, this vago,vagal reflex may involve an excitatory interneurone between the NTS and DMV vagal inhibitory output. [source]


Contractile Changes of the Clitoral Cavernous Smooth Muscle in Female Rabbits with Experimentally Induced Overactive Bladder

THE JOURNAL OF SEXUAL MEDICINE, Issue 5 2008
Soon-Chul Myung MD
ABSTRACT Introduction., Recently, growing clinical evidence has suggested that sexual dysfunction is more prevalent in women with overactive bladder (OAB). Aims., However, there has been no basic research to clarify the relationship between OAB and female sexual dysfunction. Therefore, we investigated this issue using a rabbit model of OAB. Methods., Twenty-seven New Zealand white female rabbits were randomly divided into the OAB and control groups. Main Outcome Measures., The contractile responses of clitoral cavernous strips to K+, phenylephrine (PE), Bay K 8644, and endothelin (ET)-1, and the relaxation responses of acetylcholine (ACh), sodium nitroprusside (SNP), and Y-27632 to PE-induced contraction by measuring isometric tension. Results., The contractile responses to K+, PE, Bay K 8644, and ET-1 were significantly more increased in the OAB group in a dose-dependant manner than in the control group (P < 0.05), and the responses to ET-1 were more prominent than those to the remaining substances (P < 0.01). The increased contractile responses to ET-1 were blocked by BQ123 (ETA receptor antagonist) but not by BQ788 (ETB receptor antagonist). Clitoral cavernosal strips from the OAB group were more difficult to relax than those from the control group in terms of ACh- and SNP-induced relaxation (P < 0.05). The Y-27632-induced relaxant responses to PE- and ET-1-induced contraction were less prominent in the OAB group than in the control group. Conclusions., The results of this study provide evidence that female OAB may deteriorate clitoral engorgement, which is associated with a greater force generation by increased calcium sensitization and subsequently decreased of relaxation. The activation of ET and Rho-kinase system may be crucial to negatively effect the clitoral smooth muscle relaxation in experimentally induced OAB animal model. But whether these vasomotor effects are revived in human clitoris is still debatable. Myung S-C, Lee M-Y, Lee S-Y, Yum S-H, Park S-H, and Kim S-C. Contractile changes of the clitoral cavernous smooth muscle in female rabbits with experimentally induced overactive bladder. J Sex Med 2008;5:1088,1096. [source]


The Effect of Ovariectomy on Rat Vaginal Tissue Contractility and Histomorphology

THE JOURNAL OF SEXUAL MEDICINE, Issue 2 2006
F. Fatih Önol MD
ABSTRACT Introduction., Ovarian hormones have an important role in age-related genital arousal disorders; however, our knowledge regarding possible vaginal wall morphology and contractility changes in low-hormonal states is limited. Aims., To investigate morphological and functional alterations in the vaginal tissue in a rat ovariectomy model and to show the differences between proximal and distal vagina. Methods., Six weeks following ovariectomy, vaginal tissues were examined under light and electron microscopy. Circularly cut distal and proximal tissues were studied in the organ bath under isometric tension and compared with age-matched controls. Contractile responses to electrical field stimulation (EFS), phenylephrine, carbachol, and the effects of alpha-1 and alpha-2 blockade on EFS-induced contractility were investigated. Relaxation responses to EFS and vardenafil were investigated in precontracted strips. Main Outcome Measures., Differences between control and ovariectomy groups in terms of vaginal tissue contractility and histomorphological properties. Results., Distal vagina showed different epithelial characteristics and a better-developed muscularis compared with proximal vagina. Ovariectomy caused thinning of the epithelium, severe degeneration in epithelial architecture, and smooth muscle atrophy. Contraction and relaxation responses of distal strips were significantly lower in ovariectomized rats. Contractile responses to neuropharmacological stimulation were insignificant in proximal strips of both groups. EFS-induced contractions in distal strips diminished significantly after alpha-1 and alpha-2 adrenergic blockade. EFS caused frequency-dependent relaxation responses in precontracted distal strips, which were significantly decreased after nitric oxide synthase inhibition. Conclusions., Ovariectomy causes significant alteration in rat vaginal tissue morphology and contractility. Contraction and relaxation responses of distal vagina are significantly greater compared with morphologically distinct proximal vagina. Alpha-1 and alpha-2 receptors are the main mediators of contraction in distal rat vaginal tissue whereas nitric oxide pathway may have at least a partial role in relaxation. Main mediators of the rat vaginal tissue relaxation and the effect of ovariectomy on this regulation are yet to be defined. Önol FF, Ercan F, and Tarcan T. The effect of ovariectomy on rat vaginal tissue contractility and histomorphology. J Sex Med 2006;3:233,241. [source]


The effects of selective phosphodiesterase III and V inhibitors on adrenergic and non-adrenergic, non-cholinergic relaxation responses of guinea-pig pulmonary arteries

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 2 2003
A. Tasatargil
Summary 1 The aim of the present study was to investigate the role of several possible neurotransmitters in mediating non-adrenergic, non-cholinergic (NANC) relaxation, and the effects of phosphodiesterase (PDE) III and V inhibitors on adrenergic and NANC relaxation in branch pulmonary artery (PA) of guinea-pig. 2 Under the NANC conditions, electrical field stimulation (EFS, 60 V, 0.2 ms, 20 Hz) induced a tetrodotoxin-sensitive relaxation of the histamine-precontracted PA rings. The nitric oxide (NO) synthase inhibitor NG -nitro- l -arginine methyl ester (l -NAME, 10,4 m) and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10,5 m) partially inhibited the EFS-induced relaxation. The inhibitory effect of l -NAME was reversed completely by l -arginine (10,3 m), but not d -arginine (10,3 m). 3 This NANC relaxation was attenuated by 8-phenyltheophylline (10,5 m), a P1 -purinoceptor antagonist. 4 The NANC response was potentiated by 10,6 m zaprinast, a type V PDE inhibitor, but was unaffected by 3 × 10,6 m milrinone, a type III PDE inhibitor. 5 Sodium nitroprusside (SNP) caused a concentration-dependent vasodilator effect which was potentiated by zaprinast, but unaffected by milrinone. Moreover, the effect of combination of zaprinast with milrinone was not significantly different from that observed with zaprinast alone. 6 Isoprenaline produced a concentration-dependent vasodilatation in branch PA of guinea-pig which was potentiated by both zaprinast and milrinone, the efficacy of milrinone being greater than zaprinast. 7 These results suggest that both nitrergic and purinergic pathways are involved in mediating the NANC relaxation in branch PA of guinea-pig. The combination of PDE III or V inhibitors with vasorelaxant drugs may be a hopeful approach for the treatment of pulmonary hypertension. [source]


Effect of chronic renal failure on the purinergic responses of corpus cavernosal smooth muscle in rabbits

BJU INTERNATIONAL, Issue 6 2002
H. Kilicarslan
Objective ,To examine purinergic relaxation responses in chronic renal failure (CRF) in an experimental rabbit model, and thus evaluate the possible involvement of the purinergic system in erectile dysfunction with CRF. Materials and methods ,The relaxant effects of ATP were measured in strips of corpus cavernosum smooth muscle taken from control and CRF rabbits. CRF was induced in New Zealand white rabbits as previously described. Penises were excised from CRF rabbits 4 weeks after inducing uraemia. In an organ bath the strips from controls and CRF rabbit corpus cavernosum were pre-contracted with phenylephrine and increasing doses of adenosine and ATP added. Results ,In the pre-contracted rabbit cavernosal tissue the relaxations induced by adenosine and ATP were unchanged in CRF. Conclusion ,The lack of any relaxant effect of adenosine or ATP on the relaxation of cavernosal smooth muscle in rabbits with CRF might be because the relaxant effects of these agents are endothelium-independent and the endothelial purinergic receptor density was unchanged in CRF. [source]


EFFECT OF THE PHOSPHODIESTERASE 5 INHIBITORS SILDENAFIL, TADALAFIL AND VARDENAFIL ON RAT ANOCOCCYGEUS MUSCLE: FUNCTIONAL AND BIOCHEMICAL ASPECTS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2009
Haroldo A Toque
SUMMARY 1The anococcygeus muscle is part of the erectile machinery in male rodents. Phosphodiesterase (PDE) 5 inhibitors enhance and prolong the effects of cGMP, which has a key role in penile erection. The aim of the present study was to provide a functional and biochemical comparison of the three PDE5 inhibitors, namely sildenafil, tadalafil and vardenafil, in the rat anococcygeus muscle. 2Muscle strips were mounted in 4 mL organ baths and isometric force recorded. Levels of cGMP were measured using an enzyme immunoassay kit. Western blots were used to determine PDE5 protein expression. 3The PDE5 inhibitors concentration-dependently relaxed carbachol-precontracted anococcygeus muscle; however, vardenafil was more potent (pEC50 = 8.11 ± 0.05) than sildenafil (7.72 ± 0.06) or tadalafil (7.69 ± 0.05). Addition of NG -nitro- l -arginine methyl ester (100 µmol/L) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 µmol/L) to the organ baths caused significant rightward shifts in concentration,response curves for all PDE5 inhibitors. 4Sildenafil, tadalafil and vardenafil (all at 0.1 µmol/L) caused leftward shifts in the glyceryl trinitrate (GTN) concentration-response curves (by 4.0-, 3.7- and 5.5-fold, respectively). In addition, all three PDE5 inhibitors significantly potentiated relaxation responses to both GTN (0.01,10 µmol/L) and electrical field stimulation (EFS; 1,32 Hz), with vardenafil having more pronounced effects. 5All three PDE5 inhibitors reduced EFS-evoked contractions in a concentration-dependent manner over the concentration range 0.001,1 µmol/L. There were no significant differences between the effects of the three PDE5 inhibitors. 6Vardenafil (0.01,0.1 µmol/L) was more potent in preventing cGMP degradation in vitro than sildenafil (0.01,0.1 µmol/L) and tadalafil (0.01,0.1 µmol/L). 7Under control conditions, the expression of PDE5 was higher in the anococcygeus muscle than in the corpus cavernosum. 8In conclusion, PDE5 inhibitors enhance exogenous and endogenous nitric oxide-mediated relaxation in the rat anococcygeus muscle. The potency of vardenafil was greater than that of either sildenafil or tadalafil. [source]


GINKGO BILOBA EXTRACT CAUSES DECREASE IN HEART RATE IN AGED SPONTANEOUSLY HYPERTENSIVE RATS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2007
Y Kubota
SUMMARY 1We previously reported that Ginkgo biloba extract (GBE) improves cardiovascular function in young spontaneously hypertensive rats (SHR). In the present study, changes in the cardiovascular parameters of aged SHR were examined following a 4-week diet of GBE. 2Feeding with GBE significantly decreased the heart rate and blood flow velocity in the tails of aged SHR. The contractile and relaxation responses were unchanged in isolated aortas and mesenteric arteries of aged SHR fed the GBE diet. The GBE diet did not influence the protein levels of endothelial nitric oxide synthase or soluble guanylyl cyclase in the aortas. 3These findings indicate that in aged SHR, the ingestion of GBE may cause bradycardia without a beneficial effect on the vascular relaxation response. Intake of GBE as a supplement in elderly hypertensive patients should be carefully monitored. [source]


DOSE-DEPENDENT EFFECT OF CAPTOPRIL ON AORTIC REACTIVITY OF STREPTOZOTOCIN-DIABETIC RATS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2004
Tourandokht Baluchnejadmojarad
Summary 1.,Diabetes mellitus is a primary risk factor for cardiovascular disorders. Strategies that interrupt the renin,angiotensin system have been known to reduce cardiovascular disease. The present study was performed to investigate the effect of sub-chronic administration of captopril on the aortic reactivity of streptozotocin-diabetic rats. 2.,Streptozotocin-diabetic rats received captopril (30 and 50 mg/kg per day) for 2 months. Contractile responses to phenylephrine (PE) and relaxation responses to acetylcholine (ACh) and isosorbide dinitrate (ISD) were obtained from aortic rings. 3.,Concentration,response curves from captopril-treated diabetic rats to PE were attenuated compared with vehicle (Saline)-treated diabetic rats, especially at a dose of 50 mg/kg captopril. In addition, endothelium-dependent relaxation responses induced by ACh were significantly higher in captopril-treated diabetic rats compared with diabetic rats. The endothelium-independent relaxation responses for ISD were found not to be significantly different among the groups. 4.,Therefore, sub-chronic treatment of diabetic rats with captopril in a dose-dependent manner could prevent the functional changes in vascular reactivity in diabetic rats. [source]


Alcohol And Endothelial Function: A Brief Review

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2001
IB Puddey
SUMMARY 1. In spite of the dose-related effects of alcohol consumption to increase blood pressure, regular light to moderate alcohol intake appears to confer protection against both coronary artery disease and ischaemic stroke. In contrast, heavy alcohol consumption increases the risk of coronary artery disease and the risk of both haemorrhagic and ischaemic stroke. 2. Effects of alcohol consumption on endothelial cell function may be relevant to these disparate effects on cardiovascular outcomes. In in vitro animal studies, low doses of alcohol have been demonstrated to increase release of nitric oxide and augment endothelium-mediated vasodilatation, whereas higher doses impair endothelium-dependent relaxation responses. In contrast, chronic administration of alcohol to rats has generally been associated with tolerance to the acute inhibitory effects of alcohol on endothelium-mediated vasodilatation and may even result in augmentation of such responses. 3. The few human studies to date that have examined the effects of alcohol on endothelial function have focused on postischaemic flow-mediated dilation of the brachial artery (FMD). Although blunted FMD responses have been reported in alcoholic subjects, acute administration of alcohol or short-term interventions to reduce alcohol intake have had no effect to either improve or impair FMD. 4. Further studies in humans assessing acute and longer term dose-related effects of alcohol on endothelial function in both conduit and resistance vessels will be necessary if the relevance of the findings from in vitro and in vivo animal studies are to be understood in the context of the complex interrelationships of alcohol with cardiovascular disease. [source]