Clinical and functional correlates of platelet cyclic GMP in essential hypertensives

Background: Platelets play a central role in atherothrombosis which is responsible of major cardiovascular complications in human hypertension. Nitric oxide (NO) inhibits platelet aggregation via the second messenger cyclic GMP (cGMP). In essential hypertensives (EHs), we examined the relationship between platelet cGMP and clinical, hemodynamic, humoral variables as well as the responses to aggregating agents. Methods: In untreated EHs (M/F 106/43, age 44.4±1.1 yr, smokers Y/N 38/111) blood pressure, heart rate and stroke volume (impedance cardiography) were assessed after supine rest and venous blood was sampled for platelet cGMP (radioimmunoassay on acid extracts of washed platelets), plasma cGMP, atrial natriuretic peptide, renin activity, aldosterone and platelet aggregation to epinephrine (EPI, 5 µM) and ADP 4 µM (optical aggregometry on platelet rich plasma). Results: Platelet cGMP (7.0±0.3 pM/10^9 cells, mean±sem) was lower in males and smokers than in their counterparts (p<0.01 for both). Among the variables tested, platelet cGMP was related to cigarettes number (–0.21), HDL cholesterol (r=0.32), aldosterone (r= –0.21) and hemoglobin (–0.16); in a multivariate analysis including also sex, HDLc was the best predictor of platelet cGMP. The aggregating response to EPI (r= –0.28), but not to ADP (r= –0.07, ns) was inversely related to platelet cGMP levels. Conclusions: Cyclic GMP in resting platelets of EHs is positively predicted by HDL cholesterol and is inversely related to the aggregating response to epinephrine. It is suggested that a defect of the platelet NO/cGMP system could identify uncomplicated EHs at higher risk of thrombotic events during surges of sympathetic activity.