Nitric oxide lowers the calcium sensitivity of tension in the rat tail artery.
1. Controversy exists as to whether a fall in the intracellular Ca2+ concentration ([Ca2+]i) is a requisite element of the vasodilatory response to nitric oxide (NO). 2. We studied the effect of NO on the coupling between [Ca2+]i and vasoconstriction in arterial segments loaded with the [Ca2+]i-sensitive, intracellular dye fura-2. As data interpretation is equivocal when fura-2 is loaded into both endothelial and smooth muscle cells, we compared results from in vitro experiments on segments of the rat tail artery in which fura-2 and noradrenaline were applied on the luminal or adventitial side, and endothelium was removed 'physically' (rubbing or air) or 'functionally' (Nomega-nitro-L-arginine methyl ester). The use of air perfusion to remove endothelium is of considerable benefit since it allows paired observations in a single tissue. 3. Fura-2 loaded into endothelial cells but endothelial 'contamination' of the smooth muscle cell [Ca2+]i signal was minimal. 4. Endogenous NO decreased vasoconstrictor responses to noradrenaline but had no effect on [Ca2+]i. 5. Nitroglycerine decreased vasoconstrictor responses in a concentration-dependent fashion but had no effect on [Ca2+]i. 6. In conclusion, NO causes vasodilatation via a mechanism which is downstream of [Ca2+]i mobilization.
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Laboratoire de Pharmacologie Cardio-vasculaire, Faculte de Pharmacie, Universite Henri Poincare-Nancy I, 5 rue Albert Lebrun, 54001 Nancy Cedex, France.
Spitzbarth
E
E
Robert
A
A
Giummelly
P
P
Atkinson
J
J
Capdeville-Atkinson
C
C
D000388:Air; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000098:blood supply*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D002118:Calcium; D016257:Fura-2; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine