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Relaxation induced by acetylcholine involves endothelium-derived hyperpolarizing factor in 2-kidney 1-clip hypertensive rat carotid arteries.

Ana Paula Sendão Oliveira·Lusiane M Bendhack
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Abstract

Acetylcholine induced relaxation in a concentration-dependent way in isolated phenylephrine-contracted carotid artery rings from normotensive two-kidney (2K) and hypertensive two-kidney one-clip (2K-1C) rats. In the presence of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NOARG, 100 micromol/l), the relaxation stimulated with acetylcholine was blocked in 2K arteries. However, in 2K-1C arteries, the relaxation was only partially inhibited. Indomethacin (3 micromol/l) had no effect in both groups. In 2K arteries, the combination of L-NOARG and indomethacin had similar effects to L-NOARG alone. On the other hand, in 2K-1C arteries, indomethacin further inhibited the maximum effect induced by acetylcholine. Endothelium-dependent relaxation induced by acetylcholine was markedly reduced in 2K arteries contracted with 90 mmol/l KCl, and it was abolished in 2K-1C arteries. The remaining response to acetylcholine in 2K arteries was blocked by L-NOARG. Thus, in addition to NO, a relaxing factor sensitive to extracellular K+ changes in the membrane potential contributes to endothelium-dependent relaxation in 2K-1C rat carotid artery. On the other hand, in arteries from 2K rats, only NO is involved in the relaxation induced by acetylcholine. The combination of 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 3 micromol/l), indomethacin (3 micromol/l) and L-NOARG (100 micromol/l) reduced the relaxation induced by acetylcholine in arteries from 2K-1C rats contracted with phenylephrine. On the other hand, in 2K arteries, the relaxation induced by acetylcholine was abolished. The combination of ODQ and K+ channel blockers charybdotoxin (100 nmol/l), apamin (500 nmol/l) and 4-aminopyridine (1 micromol/l) abolished the relaxation induced by acetylcholine in 2K and 2K-1C carotid arteries. These data indicate that the endothelium-derived relaxing factors that contribute to relaxation induced by acetylcholine are different in 2K and 2K-1C arteries. In 2K arteries, the only factor is NO, which involves the activation of K+ channels and the cGMP pathway. However, in 2K-1C arteries, the relaxation induced by acetylcholine is dependent on NO in addition to another factor, which is insensitive to indomethacin, but also activates the K+ channels and the cGMP pathway, presumably by membrane hyperpolarization through endothelium-derived hyperpolarizing factor.

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AcetylcholineAnimalsBiological FactorsCarotid ArteriesCyclic GMPCyclooxygenase InhibitorsEnzyme InhibitorsEpoprostenolHemoglobinsHypertension, RenovascularIndomethacinMaleMuscle ContractionMuscle, Smooth, VascularNerve Tissue ProteinsNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type INitroarginineOxadiazolesPotassium Channel BlockersPotassium ChlorideQuinoxalinesRatsRats, WistarVasodilator AgentsJournal ArticleResearch Support, Non-U.S. Gov't

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BibTeXRIS

Ana Paula Sendão Oliveira, Lusiane M Bendhack. 2004. Relaxation induced by acetylcholine involves endothelium-derived hyperpolarizing factor in 2-kidney 1-clip hypertensive rat carotid arteries.. https://doi.org/10.1159/000080378

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