Platelet cyclic AMP in essential hypertension.
Various abnormalities in platelet metabolism, including increased sensitivity to several aggregating agents, have been described in essential hypertension. Platelet response is controlled by Ca2+ and cyclic AMP-dependent mechanisms (stimulatory and inhibitory, respectively) which oppose one another. In the present study, the cyclic AMP contents of unstimulated platelets were measured by radio-immunoassay and observed to be lower in hypertensive than in normotensive subjects, either in the basal state or after prostaglandin E1 (PGE1) stimulation. In the presence of 7-bromo-1,5,dihydro-3,6-dimethylimidazo [2,1-b] quinazolin-2(3H)-one (Ro 15-2041), a specific inhibitor of phosphodiesterase, the increases in cyclic AMP content were similar in platelets from both groups, indicating that this enzyme was not responsible for the alterations in cyclic AMP metabolism observed in hypertension. Low external Ca2+ reduced basal and PGE1-stimulated cyclic AMP content in both normotensive and hypertensive groups but cyclic AMP levels remained lower in hypertensive patients than in normotensive subjects, indicating that Ca2+ influx is not responsible for this altered metabolism of cyclic AMP in hypertension. These data suggest that the reduced platelet cAMP content may participate in the hyperreactivity to various aggregating agents previously reported to accompany essential hypertension.
Mazeaud
M M
MM
INSERM U7, Department of Pharmacology, Hôpital Necker, Paris, France.
Le Quan Sang
K H
KH
Devynck
M A
MA
D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood*; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000494:pharmacology
D005343:Fibrinolytic Agents; D011799:Quinazolines; C046655:Ro 15-2041; D000242:Cyclic AMP; D000527:Alprostadil; D002118:Calcium