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Organ Chambers (organ + chamber)
Selected AbstractsNifedipine enhances cGMP production through the activation of soluble guanylyl cyclase in rat ventricular papillary muscleJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2005Kazuhiko Seya It is known that nifedipine, an L-type calcium channel blocker, increases cGMP production, which partially contributes to the relaxation of vascular smooth muscle. The aim of our investigation was to clarify whether or not nifedipine regulates cGMP production, which has a physiological role in cardiac muscle. To measure contractile responses and tissue cGMP levels, left ventricular papillary muscles prepared from male Wistar rats (350,400 g) were mounted in the isolated organ chamber under isometric conditions and electrically paced by means of platinum punctate electrodes (1 Hz, 1 ms duration). In papillary muscle preparation, the negative inotropic effect induced by nifedipine (30 to 300 nm) was significantly inhibited in the presence of ODQ (1H-[1,2,4]oxidazolo[4,3-a]quinoxaline-1-one; 10 ,m), a soluble guanylyl cyclase inhibitor. Furthermore, nifedipine (100 nm) strongly increased the tissue cGMP level, which was significantly decreased in the presence of ODQ. On the other hand, NG -monomethyl-l-arginine (100 ,m), a nitric oxide synthase inhibitor, did not inhibit either the negative inotropic effect or cGMP production induced by nifedipine. These results indicate that in rat left ventricular papillary muscle, nifedipine augments its negative inotropic effect at least partly through direct activation of cardiac soluble guanylyl cyclase but not nitric oxide synthase. [source] Murine in vitro whole bladder model: A method for assessing phenotypic responses to pharmacologic stimuli and hypoxiaNEUROUROLOGY AND URODYNAMICS, Issue 4 2004Joel C. Hutcheson Abstract Aims Recent advances in genetic manipulation have allowed for over expression or deletion of selective genes in mice. This offers urologic investigators new means of understanding bladder function in the context of normal development or the response to outlet obstruction. It is important to correlate any genetic manipulations in mice with specific phenotypic properties such as voiding patterns, or muscle strip physiology. We describe a simple in vivo whole bladder preparation that may be used to study the phenotypic changes in bladder function. Methods Murine bladders were mounted on a 30 gauge needle and mounted in an organ chamber containing a physiologic buffer solution. Passive bladder properties were assessed with cystometry, and active contractile responses were measured in response to electrical field stimulation and agonists. The effects of hypoxia were also studied. Results Compliance in the murine bladder is dependent upon actin myosin interactions, and increased in the presence of calcium free buffer and EGTA. The sarcoplasmic reticulum plays a smaller role in the contraction of murine bladder than in other species. Murine bladder smooth muscle demonstrated a remarkable ability to withstand hypoxia. Conclusions This simple model can be adapted to help study the murine bladder smooth muscle phenotype under highly controlled circumstances. © 2004 Wiley-Liss, Inc. [source] Effects of potassium channel opener KRN4884 on human conduit arteries used as coronary bypass graftsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2000Zhen Ren Aims The effects of a new potassium channel opener KRN4884 on human arteries have not been studied. This study was designed to investigate the effects of KRN4884 on the human internal mammary artery (IMA) in order to provide information on possible clinical applications of KRN4884 for preventing and relieving vasospasm of arterial grafts in coronary artery bypass grafting. Methods IMA segments (n = 140) taken from patients undergoing coronary surgery were studied in the organ chamber. Concentration-relaxation curves for KRN4884 were established in the IMA precontracted with noradrenaline (NA), 5-hydroxytryptamine (5-HT), angiotensin II (ANG II), and endothelin-1 (ET-1). The effect of glibenclamide (GBC) on the KRN4884-induced relaxation was also examined in NA or 5-HT-precontracted IMA. Concentration-contraction curves for the four vasoconstrictors were constructed without/with pretreatment of KNR4884 (1 or 30 µm) for 15 min. Results KRN4884 induced less relaxation (P < 0.05) in the precontraction induced by ET-1 (72.9 ± 5.5%) than by ANG II (94.2 ± 3.2%) or NA (93.7 ± 4.1%) with lower EC50 (P < 0.05) for ANG II (,8.54 ± 0.54 log m) than that for NA (,6.14 ± 0.15 log M) or ET-1 (,6.69 ± 0.34 log m). The relaxation in the IMA pretreated with GBC was less than that in control (P < 0.05). KRN4884-pretreatment significantly reduced the contraction (P < 0.05) induced by NA (151.3 ± 18.4% vs 82.7 ± 8.7%), 5-HT (82.7 ± 12.2% vs 30.1 ± 7.3%), and ANG II (24.3 ± 6.3% vs 5.4 ± 1.6%), but did not significantly reduce the contraction induced by ET-1 (P > 0.05). Conclusion KRN4884 has marked vasorelaxant effects on the human IMA contracted by a variety of vasoconstrictors and the effect is vasoconstrictor-selective. [source] Blood pressure and vascular reactivity to endothelin-1, phenylephrine, serotonin, KCl and acetylcholine following chronic alcohol consumption in vitroFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2001Tijen Utkan Ethanol has been reported to cause hypertension, the mechanism of which is unknown. Therefore, the effect of chronic ethanol consumption on vascular responsiveness and blood pressure was investigated. Systolic blood pressure was recorded weekly by tail-cuff method. Aortic rings from rats fed chow ad libitum or pair-fed liquid diets containing either ethanol (7.2% v/v) or isocaloric carbohydrate for 4 weeks were placed in organ chambers for isometric tension measurement. There was a mild but significant elevation of the systolic blood pressure in the alcohol-fed rats by week 1 compared to baseline measurements and this remained higher. No significant changes in reactivity of rat isolated aortas to phenylephrine, serotonin, endothelin-1 (ET-1) and KCl were seen in chronic ethanol consumption. In addition, the sensitivity (i.e. pD2) of alcohol-fed aortic rings to the vasoconstrictors was also unchanged compared to controls. Chronic ethanol consumption, however, increased relaxation to acetylcholine with increased pD2 values, but did not alter relaxation to sodium nitroprusside, a cyclic guanosine monophosphate (cGMP)-dependent direct smooth muscle dilator. The results indicate that chronic ethanol consumption significantly potentiates endothelium-dependent relaxations in aortic rings, probably through interference with the production and/or the release of nitric oxide (NO) or adaptive alterations in muscarinic receptors on the endothelial cells, and that increased vascular responsiveness to several vasoconstrictors is not a mechanism responsible for the blood pressure elevation in the chronic alcohol consumption in rats. [source] RhoA/ROK Pathway Related to the Mechanism of Higher Susceptibility to Spasm in RA Than in IMAJOURNAL OF CARDIAC SURGERY, Issue 6 2009Xia Kun M.D. Methods: RA, IMA, and GSV that would otherwise have been discarded were collected from 25 patients who underwent coronary artery bypass grafting. Eleven matched rings of RA, IMA, and GSV were used to evaluate the vasodilatory properties of 10,7,10,4 mol/l of fasudil, a Rho-kinase inhibitor, by using in vitro organ chambers. Another 14 matched RA, IMA, and GSV were used to demonstrate the immunohistochemistry (IHC) of RhoA and mRNA of RhoA and Rho kinase. Results: The maximal vasodilation of RA to fasudil was significantly greater than IMA. RhoA protein IHC staining was different in IMA, RA, and GSV (RA > GSV >IMA). The expression of RhoA and Rho kinase mRNA in the RA was significantly greater than in the IMA. Conclusions: The expression of RhoA/Rho kinase mRNA and protein and function in the RA were significantly stronger than in the IMA, suggesting that RhoA/Rho kinase pathway may be one mechanism by which RA is more susceptible to spasm than IMA. Rho kinase inhibitors can be effective drug candidates to prevent and treat vasospasm. [source] The Novel Antioxidant, AC3056 (2,6-di-t-butyl-4-((Dimethyl-4-Methoxyphenylsilyl)Methyloxy)Phenol), Reverses Erectile Dysfunction in Diabetic Rats and Improves NO-mediated Responses in Penile Tissue from Diabetic MenTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2009Javier Angulo PhD ABSTRACT Introduction., Diabetes is associated with a high incidence of erectile dysfunction (ED) and poor response to standard treatments. Oxidative stress could be relevant in the pathophysiology of diabetic ED. Aim., To evaluate the effects of the antioxidant, AC3056 (2,6-di- t -butyl-4-((dimethyl-4-methoxyphenylsilyl)methyloxy)phenol), on diabetic ED. Methods., Erectile responses to cavernosal nerve electrical stimulation were determined in streptozotocin-induced diabetic rats. Relaxation of human corpus cavernosal (HCC) tissue and penile resistance arteries (HPRA) from human cavernosal specimens was evaluated in organ chambers and myographs, respectively. Main Outcome Measures., The influence of AC3056 on erectile responses, lipid peroxidation, and nitrite plus nitrate serum content, and nuclear factor-,B (NF-,B) expression in penile tissue, in diabetic rats, and on endothelium-dependent and neurogenic relaxation of HCC and HPRA from diabetic patients was determined. Results., Eight weeks of diabetes caused ED in rats that was prevented by oral AC3056 (0.3% w/w in rat chow) when given from the induction of diabetes. AC3056 also prevented the diabetes-induced elevation of serum thiobarbituric acid-reactive substances (TBARS), the reduction of serum nitric oxide (NO) derivatives, and the increase of NF-,B expression. Acute oral administration of AC3056 (450 mg/kg) partially reversed ED in 8-week diabetic rats. Complete reversion of ED was achieved after 3 days of treatment with 0.3% AC3056. This effect remained after 5 weeks of treatment, but it disappeared after withdrawing for 1 week. Erectile function in diabetic rats was inversely related to serum TBARS. AC3056- (30 µM) reversed endothelial dysfunction in diabetic HCC and enhanced endothelium-dependent relaxation in diabetic HPRA and significantly potentiated neurogenic relaxation of both tissues. The reduced cGMP content in HCC from diabetic patients after exposure to acetylcholine (10 µM) was corrected by AC3056 (30 µM). Conclusions., These results suggest that oxidative stress has a relevant role in pathophysiology of diabetic ED and provide a rationale for the use of antioxidant therapy in the treatment of ED in diabetes. Angulo J, Peiró C, Cuevas P, Gabancho S, Fernández A, González-Corrochano R, La Fuente JM, Baron AD, Chen KS, and Sáenz de Tejada I. The novel antioxidant, AC3056 (2,6-di-t-butyl-4-([dimethyl-4-methoxyphenylsilyl] methyloxy) phenol), reverses erectile dysfunction in diabetic rats and improves NO-mediated responses in penile tissue from diabetic men. J Sex Med 2009;6:373,387. [source] The Effect of Korean Red Ginseng Extract on the Relaxation Response in Isolated Rabbit Vaginal Tissue and Its MechanismTHE JOURNAL OF SEXUAL MEDICINE, Issue 9 2008Sun-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] Heat stress increases endothelium-dependent relaxations and prevents reperfusion-induced endothelial dysfunctionCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2002Vincent Richard Summary 1.,Heat stress has been widely used to stimulate the expression of stress proteins and is associated with various cardiovascular changes, including anti-ischaemic effects. However, the effect of heat stress on endothelial function is less clear. 2.,Heat stress was induced in anaesthetized rats by increasing body temperature to 42°C for 15 min. Twenty-four hours later, segments of rat aorta and mesenteric and coronary arteries were mounted in organ chambers. 3.,Heat stress markedly increased relaxation to acetylcholine (ACh) in all three blood vessels studied, without affecting the response to the nitric oxide (NO) donor sydnonimine-1. 4.,Heat stress also increased aortic relaxation to histamine and the calcium ionophore A23187. 5.,In the aorta, an inhibitor of NO synthesis abolished the response to ACh in both control and heat stressed-rings, whereas a cyclo-oxygenase inhibitor had no effect. 6.,Heat stress also prevented completely the impaired response to ACh in coronary arteries isolated from rats subjected to myocardial ischaemia and reperfusion. 7.,Thus, heat stress increases the stimulated release of NO the rat aorta and mesenteric and coronary arteries and prevents reperfusion-induced injury at the level of the coronary endothelium. [source] Acute And Chronic Sympathoinhibition On Carotid Artery Diameter Of Spontaneously Hypertensive Rats: Effects Of Clonidine And FlesinoxanCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2000H Dabiré SUMMARY 1. Hypertensive conduit arteries are thicker and stiffer than those of normotensive controls. Whether they are specifically sensitive to central sympathoinhibition has never been investigated. 2. The effects of acute (24 h infusion) and chronic (4 week infusion) treatments with clonidine (0.01 and 0.1 mg/kg per day) and flesinoxan (1 and 3 mg/kg per day) on carotid artery diameter were investigated in spontaneously hypertensive rats. At the end of treatment, blood pressure (BP) was recorded in the rats while they were conscious. Rats were then anaesthetized for carotid artery diameter measurements using an ultrasonic echo-tracking device. 3. In conscious rats, clonidine significantly decreased BP and heart rate (HR) following acute but not chronic treatment. In contrast, flesinoxan significantly decreased BP following both the acute and chronic treatment. In anaesthetized animals, the two agents have opposite effects on isobaric carotid artery diameter, with a decrease under clonidine and an increase under flesinoxan. After 4 weeks infusion, the reactivity of aortic rings was studied in organ chambers. Flesinoxan, but not clonidine, caused the relaxation of potassium chloride precontracted aortic segments. 4. The results indicate that although clonidine and flesinoxan are centrally acting antihypertensive agents, the drug-induced changes in isobaric carotid diameter may be influenced by local factors independent of the central action of the two drugs. [source] | ||||||||||