Home About us Contact
|
Home About us Contact | ||
|
|
||
Relaxant Effects (relaxant + effects)
Selected AbstractsRelaxant effects of , -adrenergic agonists on porcine and human detrusor muscleACTA PHYSIOLOGICA, Issue 2 2005J. K. Badawi Abstract Aim:, Relaxant effects of different , -adrenoceptor agonists on porcine and human detrusor were examined. Thus, the , -adrenoceptor subtype mainly responsible for relaxation in the detrusor muscle of pigs was characterized. Additionally, different effects of several , -agonists in both species were shown. Methods:, Experiments were performed on muscle strips of porcine and human detrusor suspended in a tissue bath. The relaxant effects of the non-selective , -agonist isoprenaline, the selective ,2-agonists procaterol, salbutamol and the selective ,3-agonists BRL 37344, CL 316 243 and CGP 12177 on potassium-induced contraction were investigated. The inhibitory effect of different substances on the maximum contraction and the rank order of potency for endogenous catecholamines was determined in pigs. Furthermore, concentration-relaxation curves were performed for pigs and humans. Results:,Pigs: In the pre-treatment experiments isoprenaline and procaterol showed similar effects. The concentration,response experiments showed that the maximum relaxation induced by procaterol and salbutamol was more than 90%, not significantly different from isoprenaline, whereas the maximum relaxations of CL 316 243, BRL 37344 and CGP 12177 amounted to 68, 70 or 30%, respectively. Rank order of potencies was isoprenaline , adrenaline > noradrenaline. Humans: Isoprenaline, procaterol, salbutamol and CL 316 243 showed a maximum relaxation of 80, 41, 24 and 35% and pD2 values of 6.24, 5.65, 5.48 and 5.55, respectively. Conclusion:,,2-receptors play a main functional role in mediating relaxation of porcine detrusor. Selective ,2- and ,3-agonists similarly relax the human detrusor. Effects were smaller compared with the pig. [source] Xanthine-analog, KMUP-2, enhances cyclic GMP and K+ channel activities in rabbit aorta and corpus cavernosum with associated penile erectionDRUG DEVELOPMENT RESEARCH, Issue 3 2002Rong-Jyh Lin Abstract The pharmacological properties of KMUP-2 were examined in isolated rabbit aorta and corpus cavernosum smooth muscle (CCSM). KMUP-2 caused relaxations that were attenuated by removed endothelium, high K+, and pretreatment with the soluble guanylate cyclase (sGC) inhibitors methylene blue (10 ,M) and ODQ (1 ,M), a NOS inhibitor, L-NAME (100 ,M), a K+ channel blocker TEA (10 mM), a KATP channel blocker glibenclamide (1 ,M), a voltage-dependent K+ channel blocker 4-AP (100 ,M), and the Ca2+ -dependent K+ channel blockers apamin (1 ,M) and charybdotoxin (ChTX, 0.1 ,M). The relaxant responses of KMUP-2 (0.01, 0.05, 0.1 ,M) together with a PDE inhibitor, IBMX (0.5 ,M), had additive effects on rabbit aorta and CCSM. Additionally, KMUP-2 (100 ,M) also affected cGMP metabolism, due to its inhibiting activity on PDE in human platelets. KMUP-2 (0.1,100 ,M) further induced an increase of intracellular cGMP levels in the primary cultured rabbit aortic and CCSM cells. These increases in cGMP content were abolished in the presence of methylene blue (100 ,M) and ODQ (10 ,M). Obviously, the relaxant effects of KMUP-2 on rabbit isolated tissues are more sensitive in CCSM than in aorta. Moreover, KMUP-2 also stimulated NO/sGC/cGMP pathway and subsequent elevation of cGMP by blockade of PDE and enhanced opening of K+ channels in rabbit aorta and CCSM. KMUP-2 (0.2, 0.4, 0.6 mg/kg), similar to KMUP-1 and sildenafil, caused increases of intracavernous pressure (ICP) and duration of tumescene (DT) in a dose-dependent manner. It is concluded that both the increases of cGMP and the opening activity of K+ channels play prominent roles in KMUP-2-induced aortic smooth muscle and CCSM relaxation and increases of ICP in rabbits. Drug Dev. Res. 55:162,172, 2002. © 2002 Wiley-Liss, Inc. [source] Gastrointestinal, selective airways and urinary bladder relaxant effects of Hyoscyamus niger are mediated through dual blockade of muscarinic receptors and Ca2+ channelsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2008Anwarul Hassan Gilani Abstract This study describes the spasmolytic, antidiarrhoeal, antisecretory, bronchodilatory and urinary bladder relaxant properties of Hyoscyamus niger to rationalize some of its medicinal uses. The crude extract of H. niger seeds (Hn.Cr) caused a complete concentration-dependent relaxation of spontaneous contractions of rabbit jejunum, similar to that caused by verapamil, whereas atropine produced partial inhibition. Hn.Cr inhibited contractions induced by carbachol (1 ,m) and K+ (80 mm) in a pattern similar to that of dicyclomine, but different from verapamil and atropine. Hn.Cr shifted the Ca2+ concentration,response curves to the right, similar to that caused by verapamil and dicyclomine, suggesting a Ca2+ channel-blocking mechanism in addition to an anticholinergic effect. In the guinea-pig ileum, Hn.Cr produced a rightward parallel shift of the acetylcholine curves, followed by a non-parallel shift with suppression of the maximum response at a higher concentration, similar to that caused by dicyclomine, but different from that of verapamil and atropine. Hn.Cr exhibited antidiarrhoeal and antisecretory effects against castor oil-induced diarrhoea and intestinal fluid accumulation in mice. In guinea-pig trachea and rabbit urinary bladder tissues, Hn.Cr caused relaxation of carbachol (1 ,m) and K+ (80 mm) induced contractions at around 10 and 25 times lower concentrations than in gut, respectively, and shifted carbachol curves to the right. Only the organic fractions of the extract had a Ca2+ antagonist effect, whereas both organic and aqueous fractions had anticholinergic effect. A constituent, ,-sitosterol exhibited Ca2+ channel-blocking action. These results suggest that the antispasmodic effect of H. niger is mediated through a combination of anticholinergic and Ca2+ antagonist mechanisms. The relaxant effects of Hn.Cr occur at much lower concentrations in the trachea and bladder. This study offers explanations for the medicinal use of H. niger in treating gastrointestinal and respiratory disorders and bladder hyperactivity. [source] Evidence against ,2 -adrenoceptors mediating relaxation in rat thoracic aortae: ,2 -agonists relaxation depends on interaction with ,1 -adrenoceptorsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2006Enrique F. Castillo Abstract In rat aorta, the presence of functional ,2 -adrenoceptors (,2 -AR) was investigated in ring preparations preconstricted with ,1 -adrenergic and non- ,1 -adrenergic agonists. Particularly, the hypothetical interference of ,2 -AR agonists with ,1 -AR-mediated vasoconstriction was evaluated. Relaxant and contractile responses to ,2 -AR agonists were obtained. In endothelium-intact and endothelium-denuded aortic rings preconstricted with phenylephrine (1 × 10,6 m), the imidazoline derivatives, clonidine and UK14304, induced relaxations with similar order of potencies (,log EC50) and maxima relaxant effects respectively. Pretreatment with the NO synthase inhibitor, NG -nitro- l -arginine methyl ester (l -NAME) had no effect on the relaxant responses to clonidine and UK14304. In phenylephrine-constricted rings with endothelium, relaxations to clonidine and UK 14304 were not antagonized by the selective ,2 -AR antagonist, rauwolscine (,1 × 10,6 m). Clonidine and UK 14304 induced only contractions on endothelium-intact and endothelium-denuded aortic rings contracted with prostaglandin F2, (3 × 10,7 m). Moreover, clonidine and UK 14304-induced relaxation of endothelium-denuded arteries precontracted with methoxamine but not with serotonin. Finally, the concentration,contraction curves to clonidine and UK 14304 in endothelium-denuded aortic rings were significantly shifted to the right by the ,1D -AR selective antagonist, BMY 7378, and rauwolscine. The pA2 and pKB values for BMY 7378 and rauwolscine, respectively, against endothelium-independent actions of clonidine and UK 14304 were characteristic of an effect on the ,1D -AR. The other selective ,2 -AR agonist tested BHT 933 (an azepine derivative), lacks considerable relaxant and contractile effects in rat aorta. The results provide no evidence for the presence of functional ,2 -AR in rat aorta. Respectively, the relaxant and contractile effects of the imidazoline derivatives, clonidine and UK 14304, may be due to an adjustable (in relation to the agonist-dependent active state of the ,1 -AR), inhibitory and excitatory, interaction with ,1 -ARs. [source] Gender differences in drug effects: implications for anesthesiologistsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2003H. Pleym Background:, The gender aspect in pharmacokinetics and pharmacodynamics of anesthetics has attracted little attention. Knowledge of previous work is required to decide if gender-based differences in clinical practice is justified, and to determine the need for research. Methods:, Basis for this paper was obtained by Medline searches using the key words ,human' and ,gender' or ,sex,' combined with individual drug names. The reference lists of these papers were further checked for other relevant studies. Results:, Females have 20,30% greater sensitivity to the muscle relaxant effects of vecuronium, pancuronium and rocuronium. When rapid onset of or short duration of action is very important, gender-modified dosing may be considered. Males are more sensitive than females to propofol. It may therefore be necessary to decrease the propofol dose by 30,40% in males compared with females in order to achieve similar recovery times. Females are more sensitive than males to opioid receptor agonists, as shown for morphine as well as for a number of kappa (OP2) receptor agonists. On this basis, males will be expected to require 30,40% higher doses of opioid analgesics than females to achieve similar pain relief. On the other hand, females may experience respiratory depression and other adverse effects more easily if they are given the same doses as males. Conclusion:, These examples illustrate that gender should be taken into account as a factor that may be predictive for the dosage of several anesthetic drugs. Moreover, there is an obvious need for more research in this area in order to further optimize drug treatment in anesthesia. [source] Relaxant responses to calcium channel antagonists and potassium channel opener in human saphenous veinAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2006C. Ford Summary 1 As shown in a parallel study the magnitude of depolarization induced in human saphenous vein by raising external potassium ([K+]e) falls markedly below the theoretical values predicted by the Goldman,Hodgkin,Katz equations. This anomaly prompted us to re-examine the relaxant actions of L-type (nifedipine) and T-type (mibefradil) Ca2+ channel antagonists, and relaxant and electrophysiological effects of the K+ channel opener, pinacidil, on saphenous veins contracted by the elevation of [K+]e. 2 Nifedipine produced concentration,dependent relaxations in tissues contracted at various high [K+]e. In tissues contracted with 20 mm [K+]e, the pIC50 for nifedipine was significantly (8.20 ± 0.05; n = 6; mean ± SEM; P < 0.05) greater than in tissues contracted with ,40 mm [K+]e. 3 Tissues contracted with 20 mm [K+]e also relaxed in response to mibefradil (pIC50 = 6.1 ± 0.14) and pinacidil (pIC50 = 6.45 ± 0.08), the latter being almost completely reversed (93.4 ± 9.9%) by addition of glibenclamide (10 ,m). 4 The resting Em of smooth muscle cells of saphenous vein was ,77.0 ± 0.7 mV (n = 52), and 20 mm [K+]e produced a modest but significant depolarization to ,73.0 ± 0.7 mV (n = 52). Incubation with pinacidil plus 20 mm [K+]e resulted in a significant hyperpolarization of the Em to ,82 ± 0.6 mV (n = 52). 5 N, -nitro- l -arginine methyl ester did not impede the relaxant responses of nifedipine, mibefradil or pinacidil. 6 In conclusion, the relaxant effects of nifedipine and pinacidil (i) occurred at an Em distinctly below the presumed threshold for the opening of the classic (CaV1.3,1) L-type Ca2+ channels, and (ii) did not depend on generation of nitric oxide. [source] Effect of chronic renal failure on the purinergic responses of corpus cavernosal smooth muscle in rabbitsBJU INTERNATIONAL, Issue 6 2002H. 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] Anandamide-induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channelsBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2001J Grainger The effects of the endocannabinoid, anandamide, and its metabolically stable analogue, methanandamide, on induced tone were examined in sheep coronary artery rings in vitro. In endothelium-intact rings precontracted to the thromboxane A2 mimetic, U46619, anandamide (0.01 , 30 ,M) induced slowly developing concentration-dependent relaxations (pEC50 [negative log of EC50]=6.1±0.1; Rmax [maximum response]=81±4%). Endothelium denudation caused a 10 fold rightward shift of the anandamide concentration-relaxation curve without modifying Rmax. Methanandamide was without effect on U46619-induced tone. The anandamide-induced relaxation was unaffected by the cannabinoid receptor antagonist, SR 141716A (3 ,M), the vanilloid receptor antagonist, capsazepine (3 and 10 ,M) or the nitric oxide synthase inhibitor, L -NAME (100 ,M). The cyclo-oxygenase inhibitor, indomethacin (3 and 10 ,M) and the anandamide amidohydrolase inhibitor, PMSF (70 and 200 ,M), markedly attenuated the anandamide response. The anandamide transport inhibitor, AM 404 (10 and 30 ,M), shifted the anandamide concentration-response curve to the right. Precontraction of endothelium-intact rings with 25 mM KCl attenuated the anandamide-induced relaxations (Rmax=7±7%), as did K+ channel blockade with tetraethylammonium (TEA; 3 ,M) or iberiotoxin (100 nM). Blockade of small conductance, Ca2+ -activated K+ channels, delayed rectifier K+ channels, KATP channels or inward rectifier K+ channels was without effect. These data suggest that the relaxant effects of anandamide in sheep coronary arteries are mediated in part via the endothelium and result from the cellular uptake and conversion of anandamide to a vasodilatory prostanoid. This, in turn, causes vasorelaxation, in part, by opening potassium channels. British Journal of Pharmacology (2001) 134, 1003,1012; doi:10.1038/sj.bjp.0704340 [source] Effect of caffeine on response of rabbit isolated corpus cavernosum to high K+ solution, noradrenaline and transmural electrical stimulationCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2004Adebowale Adebiyi Summary 1.,Caffeine has wide-ranging activities on smooth muscles, including contractile and relaxant effects. The aim of the present study was to examine the activity of caffeine on rabbit corpus cavernosum (RCC). 2.,The effects of caffeine (0.5,4.0 mmol/L) on the response of RCC to high K+ solution, noradrenaline (NA) and transmural electrical stimulation (EFS) were studied in a tissue bath system. 3.,Caffeine did not contract the RCC. However, 0.5,4.0 mmol/L caffeine caused concentration-dependent relaxation of tension development in high-K+ (120 mmol/L) solution in contrast with the solvent control. At 4.0 mmol/L caffeine, high-K+ solution-induced tone of the RCC was reduced by 73.4 ± 7.3%. Caffeine (0.5,4.0 mmol/L) also concentration-dependently relaxed NA (12.5 µmol/L)-induced tonic contraction of the RCC. At 4.0 mmol/L caffeine, NA-induced tone of the RCC was reduced by 41.1 ± 7.0%. Incubation of RCC in 2.0 mmol/L caffeine for 30 min prior to EFS (1,40 Hz) caused a marked rightward shift in the frequency,response curve. 4.,The results of the present study suggest that caffeine exhibits relaxant activity on rabbit cavernosal smooth muscle and the mechanism of this activity possibly involves inhibition of Ca2+ signalling. [source] | ||||||||||