Contribution of nitric oxide to the endothelium-dependent hyperpolarization in rat aorta.
1. The effect of endogenous and exogenous nitric oxide on the membrane potential (Em) of smooth muscle cells of the thoracic aorta of rats was investigated. 2. In tissues with intact endothelium, application of ACh or carbachol generated a change of the membrane potential consisting of an initial hyperpolarization by 10-12 mV, followed by a partial recovery toward a level which was at 10 min still 6-8 mV more negative than in control conditions. 3. Application of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of endogenous NO production, had no significant effect on the resting membrane potential. The initial peak endothelium-dependent hyperpolarization elicited by ACh or carbachol was not significantly diminished. However, the recovery was more accentuated. Similarly, NG-monomethyl-L-arginine (L-NMMA) significantly diminished the second component of the endothelium-dependent hyperpolarization without affecting the magnitude of the first transient peak Em change. 4. Nitroglycerin produced a small sustained hyperpolarization of 1-2 mV, and the NO donor SIN-1, the active metabolite of molsidomine, similarly increased Em by about 1 mV. Infusion of high doses of acidified NaNO2 solution caused a hyperpolarization smaller than that evoked by ACh or carbachol. 5. 8-Bromo-cyclic GMP caused little change of membrane potential. In the presence of 8-Br-cGMP, ACh evoked a membrane electrical response similar to that observed in the absence of the nucleotide. 6. It is concluded that, in the rat aorta, the initial peak endothelium-dependent hyperpolarization observed under the influence of ACh or carbachol is not directly related to the synthesis of NO.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology and Physiopathology, University of Gent, Belgium.
B
B
Vanheel
J
J
Van de Voorde
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I
Leusen
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D002217:Carbachol; D001120:Arginine; D005996:Nitroglycerin; D006152:Cyclic GMP; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester