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.
University of Glasgow, Department of Medicine and Therapeutics, Western Infirmary, UK.
N
N
Thorin-Trescases
C A
CA
Hamilton
E
E
Jardine
J L
JL
Reid
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction; D014661:Vasoconstriction
D016232:Endothelins; D007295:Inositol Phosphates; D002118:Calcium; D009638:Norepinephrine