Platelet cytosolic free calcium concentration in primary hypertension.
Cytosolic free Ca2+ ([Ca2+]i) concentrations were measured in platelets from hypertensive and normotensive man and rat with the fluorescent indicator Quin-2/AM, taking into account the signal of the free chelator. In the absence of added external Ca2+, no difference in [Ca2+]i was observed between platelets of hypertensive patients and those of normotensive subjects or between platelets of spontaneously hypertensive rats (SHR; Okamoto-Aoki strain) and those of normotensive Wistar-Kyoto (WKY) rats. In the presence of 0.5-1 mmol/l external Ca2+, [Ca2+]i was higher in patients with essential hypertension than in their normotensive controls (250 +/- 14 versus 198 +/- 10 nmol/l; n = 30 and 36, P < 0.01). In SHR, platelet [Ca2+]i was higher than in WKY rats but did not change with age and blood pressure. Removal of external K+ or addition of 10(-4) mol/l ouabain were used to inhibit the Na+K(+)-pump. Whereas an increase in [Ca2+]i was observed in platelets from normotensives in the absence of external K+ (273 +/- 29 versus 197 +/- 9 nmol/l; n = 6; P < 0.05), no significant change in [Ca2+]i was observed after ouabain treatment (220 +/- 2 versus 203 +/- 22 nmol/l, n = 8). These results suggest that primary hypertension is accompanied by a disequilibrium between cellular Ca2+ influx, storage and extrusion. Such a characteristic, if present in other excitable cells and in particular in vascular smooth muscle cells, may play a major role in the increase in peripheral resistance. However, the relationship between Na(+)-pump inhibition and the rise in the intracellular calcium remains unclear.
Le Quan Sang
K H
KH
Inserm U7, Department of Pharmacology, Hôpital Necker, Paris, France.
Benlian
P
P
Kanawati
C
C
Montenay-Garestier
T
T
Meyer
P
P
Devynck
M A
MA
D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D002118:Calcium