Signal transduction mechanisms of the vasoconstriction in hypertension.

We tested the hypothesis that vascular smooth muscle in genetic hypertension is characterised by hypereactivity to vasoactive agonists, by abnormalities in Ca2+ handling and the phosphoinositide signalling system. Activation of these signal transduction mechanisms by noradrenaline and endothelin-1 was compared in isolated perfused tail arteries from adult hypertensive and normotensive Wistar Kyoto rats. Basal cytosolic Ca2+ was greater in arteries from hypertensive rats, but basal perfusion pressure and basal inositol phosphate accumulation were unchanged. Contractile responses and Ca2+ mobilisation after noradrenaline, but not endothelin-1, were enhanced in arteries from hypertensive rats. Total inositol phosphates accumulation was similar in hypertensive and normotensive rats after either noradrenaline or endothelin-1 stimulation. In both hypertensive and normotensive rats, for a given Ca2+ mobilisation, higher contractile responses and higher levels of inositol phosphates were observed after endothelin-1 than noradrenaline stimulation. In conclusion, changes in contractility associated with modifications in the Ca2+ handling between hypertensive and normotensive rats suggested that alterations in the signal-transduction system occur with hypertension. The different effects of endothelin-1 and noradrenaline could be related to interactions with other signalling pathways.