Nitric oxide lowers the calcium sensitivity of tension in the rat tail artery

Abstract

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' (N(ω)-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.