Inhibition by nitroprusside of platelet calcium mobilization: evidence for reduced sensitivity to nitric oxide in essential hypertension.
OBJECTIVE
Although platelets from patients with moderate hypertension are abnormally sensitive to agonist-induced aggregation, their sensitivity to antagonists is not known. Nitric oxide (NO) is an endogenous antagonist of platelet function. The objective of this study was to determine whether platelet sensitivity to the inhibitory activity of sodium nitroprusside, a donor of NO, is abnormal in hypertension.


METHODS
Untreated patients with uncomplicated essential hypertension (mean arterial pressure > 120 mmHg) were studied. The rise in cytosolic calcium in response to 9,11-deoxy-11 alpha, 9 alpha-epoxymethanoprostaglandin F2 alpha (U46619, a thromboxane mimetic) was measured in fura-2-loaded platelets from 20 patients and 15 normotensive healthy subjects. Inhibition by sodium nitroprusside was measured in a further group of 14 patients and 20 normotensive subjects.


RESULTS
Basal cytosolic calcium concentration and the rise in this parameter induced by U46619 were significantly greater in platelets from hypertensive patients than in those from normotensive controls. The mean half-maximal inhibitory concentration of nitroprusside to calcium mobilization induced by 3 mumol/l U46619 was 3.1-fold greater in platelets from hypertensive patients than in those from controls (95% confidence interval 1.6-6.0).


CONCLUSIONS
The sensitivity of platelets to nitroprusside is reduced in essential hypertension. This reduced sensitivity to NO might influence the risk of arterial thrombosis in hypertensives.
Woods
J D
JD
Department of Clinical Pharmacology, United Medical School, Guy's Hospital, London, UK.
Edwards
J S
JS
Ritter
J M
JM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D009599:Nitroprusside; D009569:Nitric Oxide; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002118:Calcium