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

Controversy exists as to whether a fall in the intracellular Ca 2+ concentration ([Ca 2+ ] i ) is a requisite element of the vasodilatory response to nitric oxide (NO). We studied the effect of NO on the coupling between [Ca 2+ ] i and vasoconstriction in arterial segments loaded with the [Ca 2+ ] 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. Fura-2 loaded into endothelial cells but endothelial ‘contamination’ of the smooth muscle cell [Ca 2+ ] i signal was minimal. Endogenous NO decreased vasoconstrictor responses to noradrenaline but had no effect on [Ca 2+ ] i . Nitroglycerine decreased vasoconstrictor responses in a concentration-dependent fashion but had no effect on [Ca 2+ ] i . In conclusion, NO causes vasodilatation via a mechanism which is downstream of [Ca 2+ ] i mobilization.