The endothelium mediates a nitric oxide‐independent hyperpolarization and relaxation in the rat hepatic artery

Research output: Contribution to journalArticle

Abstract

The rat hepatic artery responds to acetylcholine (ACh) with an endothelium‐dependent relaxation, which is unaffected by nitric oxide (NO) synthase and cyclooxygenase inhibition. The purpose of this study was to investigate whether the NO‐independent relaxation is caused by hyperpolarization of the smooth muscle cells. In vessels with endothelium ACh induced a hyperpolarization in the presence of 0.3 mM Nw‐nitro‐l‐arginine (l‐NOARG) and 10μm indomethacin. The hyperpolarization, which slowly decayed after an initial maximum, generally lasted for at least 20 min. ACh in contrast to levcromakalim failed to hyperpolarize the smooth muscle cells in endothelium‐denuded vessels. In vessels contracted by phenylephrine (PhE) ACh caused a concentration‐dependent hyperpolarization and relaxation, and both events occurred over the same concentration interval. Curve fitting using the Hill equation showed a close correlation between the hyperpolarization and the relaxation. Exposure to a 30 mM K+ solution abolished the hyperpolarization and suppressed the relaxation induced by ACh. Nimodipine did not affect the ACh‐induced hyperpolarization, whereas the relaxation induced by ACh and levcromakalim, but not that evoked by the NO donor 3‐morpholino‐sydnonimin, were attenuated. Glibenclamide had no effect on the ACh‐induced hyperpolarization and relaxation, but abolished the corresponding responses to levcromakalim. The results demonstrate a NO‐independent hyperpolarization and relaxation in the rat hepatic artery. The hyperpolarization and relaxation were endothelium‐dependent, and apparently causally related to each other, since interference with the hyperpolarization or the subsequent effector pathway inhibited the relaxation.

Details

Authors
Organisations
External organisations
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pharmacology and Toxicology

Keywords

  • arteries, hyperpolarization, membrane potential, nitric oxide, relaxation, vascular endothelium
Original languageEnglish
Pages (from-to)375-384
JournalActa Physiologica Scandinavica
Volume152
Issue number4
Publication statusPublished - 1994 Dec
Publication categoryResearch
Peer-reviewedYes