Platelet cytosolic proton and free calcium concentrations in essential hypertension.
Alterations in the metabolism of intracellular messengers, such as calcium and cyclic adenosine 5'-phosphate (cAMP), have been reported in essential hypertension. Since intracellular pH (pHi) participates in the control of fundamental cell functions, we looked for changes in platelet cytosolic H+ concentration [( H+]i) in hypertension and investigated whether or not its impaired metabolism is linked to the calcium handling abnormalities. The fluorescent pH indicator BCECF has been used to evaluate intracellular H+ concentration in platelets, unstimulated ex vivo, from normotensive (n = 20) and hypertensive patients (n = 20). Cytosolic [H+] was 20% lower in hypertensive than in normotensive subjects (49.5 +/- 3.4 and 61.8 +/- 2.2 nmol/l cells, respectively, P less than 0.005; mean pHi values were 7.21 and 7.33, respectively). Platelet cytosolic H+ and free Ca2+ concentrations ([Ca2+]i) were determined in parallel in 15 normotensive and 15 hypertensive patients. [Ca2+]i was found to be 19% higher (P less than 0.01), and [H+]i 22% lower (P less than 0.02), in the hypertensive patients compared with the normotensive subjects. Platelet pHi and [Ca2+]i were increased simultaneously in some hypertensive patients. These results are compatible with the hypothesis of an in vivo activation of platelets in hypertension. If a similar alkalinization exists in smooth muscle cells, it may participate in cell proliferation and in an enhanced sensitivity to agonists, two parameters thought to be involved in blood pressure elevation.
Astarie
C
C
Department of Pharmacology, INSERM U7 Hôpital Necker, Paris, France.
Levenson
J
J
Simon
A
A
Meyer
P
P
Devynck
M A
MA
D000328:Adult; D001572:Benzofurans; D001792:Blood Platelets / Q000648:ultrastructure*; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000032:analysis; D005260:Female; D005452:Fluoresceins; D016257:Fura-2; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011522:Protons
D001572:Benzofurans; D005452:Fluoresceins; D011522:Protons; D006859:Hydrogen; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D002118:Calcium; D016257:Fura-2