title: Role of endothelial nitric oxide in the response to angiotensin II of small mesenteric arteries of the rat.
abstract: The role of endothelium-derived nitric oxide (NO) in the vascular contractile response to angiotensin II (Ang II) has been investigated in isolated small mesenteric resistance arteries of the rat. Both contraction and intracellular Ca2+ ion concentration ([Ca2+]i) were monitored in vessels, with and without functional endothelium, which were exposed to physiological salt solution containing 25 mM KCl. Ang II induced concentration-dependent contractile responses and increases in [Ca2+]i which, at the concentration giving the maximal response (10 nM), were not sustained in arteries with functional endothelium; however, the presence of a functional endothelium did not modify the peak responses. Ang II did not increase the cyclic guanosine 3',5'-monophosphate content of the tissue nor did it induce relaxation in arteries precontracted with 3 microM noradrenaline. The decline of the Ang II responses was suppressed by removal of the endothelium or by exposure of arteries with endothelium to either the NO synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (300 microM), or the cyclic GMP-dependent protein kinase inhibitor, Rp-8-bromoguanosine 3',5'-cyclic monophosphorothioate (30 microM). On the other hand, the NO donor SIN-1 (3-morpholino-sydnonimine, 10 microM) accelerated the decline in [Ca2+]i and contraction. These results show that endothelium-derived NO does not affect the magnitude of the phasic element of the response to Ang II, but is involved in the rapid attenuation of the tonic component. Activation of cyclic GMP-dependent protein kinase accounts for this effect of endothelium-derived NO.
authors.affiliation: Laboratoire de Pharmacologie et Physiopathologie Cellulaires, Université Louis-Pasteur de Strasbourg, Illkirch, France.
authors.forename: R
authors.initials: R
authors.lastname: Andriantsitohaina
authors.forename: L
authors.initials: L
authors.lastname: Okruhlicova
authors.forename: S F
authors.initials: SF
authors.lastname: Côrtes
authors.forename: G J
authors.initials: GJ
authors.lastname: Lagaud
authors.forename: V
authors.initials: V
authors.lastname: Randriamboavonjy
authors.forename: B
authors.initials: B
authors.lastname: Muller
authors.forename: J C
authors.initials: JC
authors.lastname: Stoclet
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013873:Thionucleotides; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D013873:Thionucleotides; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D017869:Cyclic GMP-Dependent Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D000109:Acetylcholine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine