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

Touyz, R.M. and Schiffrin, E.L. (1993) Effects of angiotensin II and endothelin-1 on platelet aggregation and cytosolic pH and free Ca2+ concentrations in essential hypertension. Hypertension, 22, pp. 853-862. (doi:10.1161/​01.HYP.22.6.853)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Touyz, R.M., and Schiffrin, E.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Hypertension
Publisher:American Heart Association
ISSN:0194-911X

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