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
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.