Vasodilator effects of sodium nitroprusside, levcromakalim and their combination in isolated rat aorta

Abstract

1 The endothelial modulation of the relaxant responses to the nitric oxide (NO) donor sodium nitroprusside (SNP) and the K ATP channel opener levcromakalim (LEM) and the interactions between these agents were analysed in isolated rat aorta. 2 LEM-induced relaxation was unchanged by endothelium removal or by the presence of L-NAME (10 74 M) or ODQ (10 76 M). In contrast, in KCl-(25 mM), but not in noradrenaline-(NA, 10 76 M) contracted arteries, SNP-induced relaxation was augmented by endothelium removal but not by L-NAME, indomethacin, glibenclamide nor charybdotoxin plus apamin. 3 The isobolographic analysis of the interactions between exogenously activated K ATP channels and cyclic GMP using mixtures of SNP and LEM revealed that there were no interactions between both drugs at the proportions at which both drugs were active. However, the points for the SNP : LEM mixtures in proportions 10 : 1 and 1 : 10,000 (i.e. at concentrations at which LEM and SNP were inactive, respectively) fell signi®cantly above the line of additivity indicating that there were negative interactions between both drugs at these selected proportions (about 5-and 2 fold inhibition, respectively). The former interaction was sensitive to glibenclamide, whereas the latter was insensitive ODQ. The magnitude of the 10 : 1 SNP : LEM interaction was smaller in endotheliumintact arteries and was absent in arteries stimulated by NA. 4 In conclusion, the relaxations induced by LEM and SNP were additive. However, the presence of endothelium and low concentrations of LEM inhibited SNP-induced relaxation. Both inhibitory eects were not additive and were only observed in KCl-and not in NA-contracted aortae.

Heparin Inhibits Contraction of Smooth Muscle Cells in Lymphatic Vessels

“…To confi rm or to exclude this mechanism of heparin action on LV, a cyclooxygenase blocker indomethacin was added to the solution 10 min before addition of heparin [10]. To confi rm or to exclude this mechanism of heparin action on LV, a cyclooxygenase blocker indomethacin was added to the solution 10 min before addition of heparin [10].…”

Endothelium-dependent and -independent vasorelaxation by a theophylline derivative MCPT: Roles of cyclic nucleotides, potassium channel opening and phosphodiesterase inhibition

“…Therefore agents those increasing both cAMP and cGMP, inhibiting phosphodiesterase and opening K + channels are able to relax agonist-induced vasoconstriction more fully (Pèrez-Vizcaíno et al, 1999). Recently, a series of xanthine-based vasodilators were synthesized in this lab and among them, KMUP-1, has been described to have cGMP increasing activity in rat aorta and rabbit carvenosa smooth muscles (Wu et al, 2001;Lin et al, 2002).…”

Characterization of a Novel, Water-Soluble Hydrogen Sulfide–Releasing Molecule (GYY4137)

“…13 Dose-response curves to NaHS were performed cumulatively while each aortic ring was exposed to a single concentration of GYY4137. In some experiments, responses to NaHS (300 mol/L) or GYY4137 (200 mol/L) were evaluated in aortic rings preincubated (30 minutes) with the K ATP channel blockers glibenclamide 14 (10 mol/L) or PNU37883A 15 (10 mol/L), the NO synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME) (50 mol/L), the cyclooxygenase inhibitor indomethacin 16 (2.8 mol/L), the soluble guanylate cyclase inhibitor ODQ 17 (3 mol/L), the adenylate cyclase inhibitor SQ23356 18 (50 mol/L), or a mixture of apamin (100 nmol/L) and charybdotoxin 19 (50 nmol/L) to block the effect of endothelium-derived hyperpolarizing factor. The effect of both NaHS and GYY4137 was also evaluated in endotheliumdenuded rings, as was the time course of effect as determined by the ability to reduce the contraction to a standard concentration of phenylephrine (200 nmol/L).…”