SIGNAL-TRANSDUCTION MECHANISMS OF THE VASOCONSTRICTION IN HYPERTENSION

We tested the hypothesis that vascular smooth muscle in genetic hypert ension is characterised by hypereactivity to vasoactive agonists, by a bnormalities in Ca2+ handling and the phosphoinositide signalling syst em. Activation of these signal transduction mechanisms by noradrenalin e and endothelin-1 was compared in isolated perfused tail arteries fro m adult hypertensive and normotensive Wistar Kyoto rats. Basal cytosol ic Ca2+ was greater in arteries from hypertensive rats, but basal perf usion pressure and basal inositol phosphate accumulation were unchange d. Contractile responses and Ca2+ mobilisation after noradrenaline, bu t 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 stimulat ion. In both hypertensive and normotensive rats, for a given Ca2+ mobi lisation, higher contractile responses and higher levels of inositol p hosphates were observed after endothelin-1 than noradrenaline stimulat ion. In conclusion, changes in contractility associated with modificat ions in the Ca2+ handling between hypertensive and normotensive rats s uggested 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.