EFFECTS OF ANGIOTENSIN-II AND ENDOTHELIN-L ON PLATELET-AGGREGATION AND CYTOSOLIC PH AND FREE CA2-HYPERTENSION( CONCENTRATIONS IN ESSENTIAL)

Citation
Rm. Touyz et El. Schiffrin, EFFECTS OF ANGIOTENSIN-II AND ENDOTHELIN-L ON PLATELET-AGGREGATION AND CYTOSOLIC PH AND FREE CA2-HYPERTENSION( CONCENTRATIONS IN ESSENTIAL), Hypertension, 22(6), 1993, pp. 853-862
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiac & Cardiovascular System
Journal title
ISSN journal
0194-911X
Volume
22
Issue
6
Year of publication
1993
Pages
853 - 862
Database
ISI
SICI code
0194-911X(1993)22:6<853:EOAAEO>2.0.ZU;2-C
Abstract
The aims of this study were to determine the relations between platele t free calcium concentrations ([Ca2+](i)), intracellular pH (pH(i)), a nd aggregation and to assess the effects of angiotensin II (Ang II) an d endothelin-1 on these platelet parameters in normotensive subjects a nd hypertensive patients. Seventeen normotensive subjects, 25 untreate d hypertensive patients, and 34 treated hypertensive patients were stu died. Platelet cytosolic free [Ca2+](i) and pH(i) were measured spectr ofluorometrically using specific fluorescent probes (fura 2-AM and BCE CF-AM, respectively) in unstimulated and Ang II- and endotheIin-1-stim ulated platelets. Aggregation was measured by a turbidometric techniqu e. 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 normoten sive (118+/-9 nmol/L, 7.11+/-0.01, respectively) and treated hypertens ive (121+/-11 nmol/L, 7.12+/-0.01, respectively) groups. In the combin ed normotensive and hypertensive groups, there were significant correl ations between [Ca2+](i) and mean arterial pressure (r=.75, P<.01), pH (i) and mean arterial pressure (r=.72, P<.01), [Ca2+](i) and pH(i) (r= .71, P<.01), [Ca2+](i) and aggregation (r=.69, P<.02), and pH(i) and a ggregation (r=.56, P<.05). Ang II stimulation significantly increased [Ca2+](i) and pH(i) in the untreated hypertensive and normotensive gro ups. The net change in [Ca2+](i) induced by Ang II was significantly h igher (P<.05) in the untreated hypertensive group compared with the ot her 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 ag gregatory responses were increased in all three groups, but the maxima l response was significantly higher in the untreated hypertensive grou p compared with the other groups (P<.05). Endothelin-1 increased pH(i) through endothelin A-receptors (effect blocked by the specific antago nist 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 conclusi on, increased Ang II-stimulated [Ca2+](i) and pH(i) in platelets of es sential hypertensive patients may be associated with increased aggrega tory responses. The stimulatory effect of endothelin-1 on pH(i) but no t on [Ca2+](i) or aggregation suggests that in platelets endothelin-in duced signaling pathways other than phospholipase C may be involved. T he significant correlations between platelet aggregation, [Ca2+](i), p H(i), and blood pressure may suggest a possible link between altered p latelet cation status and platelet function in hypertension.