Intracellular smooth muscle [Ca2+] in acetylcholine and nitric oxide-mediated relaxation of human small arteries.
In human resistance arteries the role of intracellular calcium during receptor agonist and nitric oxide (NO)-mediated vasorelaxation is almost unknown. We examined changes in smooth muscle calcium concentration ([Ca2+]i) caused by acetylcholine and the NO donor S-nitroso-N-acetylpenicillamine (SNAP) in isolated human subcutaneous small arteries. In arteries constricted with 50 mM KCl, acetylcholine and SNAP induced relaxation without any change in [Ca2+]i, whereas in noradrenaline constricted vessels, both acetylcholine and to a lesser degree also SNAP-mediated relaxation were associated with a decrease in [Ca2+]i. Furthermore incubation with SNAP (1 microM) induced a rightward shift in the [Ca2+]i-force relationship. These results suggest that relaxation mediated by endothelium derived hyperpolarizing factors (EDHF) is associated with reduction in [Ca2+]i, whereas NO-mediated relaxation can take place without changes in [Ca2+]i. This finding seems to be, at least partly, due to NO-mediated desensitization of the contractile apparatus to calcium.
Buus
Niels H
NH
Department of Pharmacology, University of Aarhus, University Park 240, DK-8000 Aarhus C, Denmark. nhbuus@dadlnet.dk
Simonsen
Ulf
U
Pilegaard
Hans K
HK
Mulvany
Michael J
MJ
D000109:Acetylcholine / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D011189:Potassium Chloride; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine