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Hypertension, Vol 22, 853-862, Copyright © 1993 by American Heart Association

ARTICLES

Effects of angiotensin II and endothelin-1 on platelet aggregation and cytosolic pH and free Ca2+ concentrations in essential hypertension

RM Touyz and EL Schiffrin
Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.

The aims of this study were to determine the relations between platelet free calcium concentrations ([Ca2+]i), intracellular pH (pHi), and aggregation and to assess the effects of angiotensin II (Ang II) and endothelin-1 on these platelet parameters in normotensive subjects and hypertensive patients. Seventeen normotensive subjects, 25 untreated hypertensive patients, and 34 treated hypertensive patients were studied. Platelet cytosolic free [Ca2+]i and pHi were measured spectrofluorometrically using specific fluorescent probes (fura 2-AM and BCECF-AM, respectively) in unstimulated and Ang II- and endothelin- 1-stimulated platelets. Aggregation was measured by a turbidometric technique. Basal [Ca2+]i (141 +/- 11 nmol/L) and pH (7.16 +/- 0.01) were higher (P < .05) in the untreated hypertensive group compared with the normotensive (118 +/- 9 nmol/L, 7.11 +/- 0.01, respectively) and treated hypertensive (121 +/- 11 nmol/L, 7.12 +/- 0.01, respectively) groups. In the combined normotensive and hypertensive groups, there were significant correlations between [Ca2+]i and mean arterial pressure (r = .75, P < .01), pHi and mean arterial pressure (r = .72, P < .01), [Ca2+]i and pHi (r = .71, P < .01), [Ca2+]i and aggregation (r = .69, P < .02), and pHi and aggregation (r = .56, P < .05). Ang II stimulation significantly increased [Ca2+]i and pHi in the untreated hypertensive and normotensive groups. The net change in [Ca2+]i induced by Ang II was significantly higher (P < .05) in the untreated hypertensive group compared with the other groups (67 +/- 6 nmol/L for the untreated hypertensive group versus 54 +/- 5 and 29 +/- 8 nmol/L for the normotensive and treated hypertensive groups, respectively). In the presence of Ang II, thrombin-induced aggregatory responses were increased in all three groups, but the maximal response was significantly higher in the untreated hypertensive group compared with the other groups (P < .05). Endothelin-1 increased pHi through endothelin A-receptors (effect blocked by the specific antagonist BQ- 123) but had no significant effect on [Ca2+]i or aggregation. However, endothelin-1 blunted thrombin-induced platelet aggregation in normotensive subjects but not in hypertensive patients. In conclusion, increased Ang II-stimulated [Ca2+]i and pHi in platelets of essential hypertensive patients may be associated with increased aggregatory responses. The stimulatory effect of endothelin-1 on pHi but not on [Ca2+]i or aggregation suggests that in platelets endothelin-induced signaling pathways other than phospholipase C may be involved.(ABSTRACT TRUNCATED AT 400 WORDS)

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