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PMID: 10618154 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Action of a NO donor on the excitation-contraction pathway activated by noradrenaline in rat superior mesenteric artery.

The Journal of physiology ·Vol. 522 Pt 1 ·2000-01-01 ·Pages 83-96

Ghisdal P, Gomez JP, Morel N

Abstract

The aim of the present study was to investigate the actions of NO donors in ratsuperior mesenteric artery stimulated with noradrenaline by studying their effects on isometric tension, membrane potential (Vm), cytosolic calcium concentration ([Ca2+]cyt) and accumulation of inositol phosphates. In unstimulated arteries, SNAP (S-nitroso-N-acetylpenicillamine, 10 microM) hyperpolarised Vm by 3.0 +/- 0.5 mV (n = 9). In KCl-stimulated arteries, SNAP relaxed contraction without changing Vm and [Ca2+]cyt. In noradrenaline-stimulated arteries, SNAP relaxed tension, repolarised Vm and decreased [Ca2+]cyt with the same potency. Responses to SNAP were unaffected by the following K+ channel blockers: glibenclamide, 4-aminopyridine, apamin and charybdotoxin, and by increasing the KCl concentration to 25 mM. In SNAP-pretreated arteries, the production of inositol phosphates and the contraction stimulated by noradrenaline were inhibited similarly. The guanylate cyclase inhibitor ODQ abolished the increase in cyclic GMP content evoked by SNAP and inhibited the effects of SNAP on contraction, Vm and accumulation of inositol phosphates in noradrenaline-stimulated artery. These results indicate that, in rat superior mesenteric arteries activated by noradrenaline, inhibition of production of inositol phosphates is responsible for the effects of the NO donor SNAP on membrane potential, [Ca2+]cyt and contraction through a cyclic GMP-dependent mechanism.

MeSH Terms
Aluminum Compounds/pharmacology Animals Calcium Signaling/drug effects Cromakalim/pharmacology Electrophysiology Fluorides/pharmacology In Vitro Techniques Inositol Phosphates/biosynthesis Male Membrane Potentials/drug effects Mesenteric Arteries/drug effects,metabolism,physiology Nitric Oxide Donors/pharmacology Norepinephrine/pharmacology Penicillamine/analogs & derivatives,pharmacology Potassium Channel Blockers Potassium Chloride/pharmacology Rats Rats, Inbred WKY S-Nitroso-N-Acetylpenicillamine Vasoconstriction Vasodilator Agents/pharmacology Vasomotor System/drug effects
Chemicals
Aluminum Compounds Inositol Phosphates Nitric Oxide Donors Potassium Channel Blockers Vasodilator Agents Cromakalim tetrafluoroaluminate Potassium Chloride S-Nitroso-N-Acetylpenicillamine Penicillamine Fluorides Norepinephrine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ghisdal P
Laboratoire de Pharmacologie, Universite Catholique de Louvain, UCL 5410, Avenue Hippocrate 54, B 1200 Bruxelles, Belgium.
Gomez J P
Morel N
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
Published
2000-01-01
Pages
83-96
Language
English
Region
England
NLM ID
0266262
PMCID
PMC2269741
Subset
IM
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