The role of nitric oxide and potassium channels in endothelium-dependent vasodilation in SHR.
We have investigated the effects of L-NG-nitro arginine (L-NOARG), glibenclamide, ouabain, tetraethylammonium and 4-aminopyridine on the methacholine-induced endothelium-dependent vasodilation in perfused resistance arteries from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Since the concentration-response curves of MCh were similar in both types of preparations there does not seem to exist an endothelial dysfunction in mesenteric arteries of SHR. L-NOARG only partially inhibited the maximal methacholine-induced response in preparations taken from SHR and WKY rats. Ouabain decreased the maximal effect of methacholine without altering the potency (pD2). Preparations from SHR were more susceptible to ouabain. 4-aminopyridine and tetraethylammonium decreased the pD2 for methacholine without reducing the maximal effect (Emax). The WKY rat preparations were more affected by these compounds. An important role of ATP-sensitive potassium channels may be ruled out since glibenclamide was without effect on the methacholine-induced vasodilation. It is concluded that endothelium-derived relaxing factor is only partially responsible for the endothelium-dependent vasodilation. Indirect arguments point toward a role of endothelium-derived hyperpolarizing factor, since ouabain, tetraethylammonium and 4-aminopyridine inhibited the methacholine-induced response. Although hypertension related differences for these compounds were observed high blood pressure does not seem to alter the functional response to muscarinic stimulation.
Hendriks
M G
MG
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
Pfaffendorf
M
M
van Zwieten
P A
PA
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D016210:Methacholine Chloride / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D010477:Perfusion; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
D001685:Biological Factors; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; C067410:endothelium-dependent hyperpolarization factor; D016210:Methacholine Chloride; D019335:Nitroarginine; D009569:Nitric Oxide; D019789:Tetraethylammonium; D001120:Arginine; D015761:4-Aminopyridine