RIDOTTA ATTIVITA' DEL SISTEMA OSSIDO NITRICO/GMP CICLICO PIASTRINICO NELL'IPERALDOSTERONISMO PRIMARIO

Rationale: Nitric oxide (NO) exerts a vasodilating effect and inhibits platelet aggregation via the second messenger cyclic GMP (cGMP). Oxidative stress associated with hypertension and major cardiovascular risk factors inhibits NO/cGMP activity. Aldosterone (Aldo) exerts a potent pressor effect via its mineralocorticoid activity; moreover, Aldo increases oxidative stress and impairs endothelial NO availability in experimental and clinical conditions. Aim:To evaluate whether also platelet NO/cGMP activity is impaired by chronic Aldo excess, we compared platelet cGMP levels in patients with primary aldosteronism (PA) and in a control group of essential hypertensives (EH). Methods: In patients with PA (n=12 males) and in EH (n=32) matched for sex, age and clinic systolic and diastolic blood pressure values (SBP, DBP), venous blood was sampled for plasma renin activity (PRA), Aldo, aldo-renin ratio (ARR), potassium (K+) and platelet cGMP (RIA on acid extracts of washed platelets) after a 60 minute supine rest. Results: PRA was lower and Aldo was higher in PA than in EH (0.1± 0.1 vs 0.4±0.1 and 25.5±8.8 vs 8.1±0.7, respectively, p<0.05), with similar SBP and DBP values. Potassium was lower in IPA than in EH (3.5±0.2 vs 4.1±.05, p<0.05) Platelet cGMP, marker of NO activity, was lower in hypokalemic patients with PA than in EH (5.1±0.4 vs 7.1±0.5 pM/10^9 platelets, p<0.05). Conclusions: These data are compatible with an impairment of the platelet NO/cGMP system in primary aldosteronism as compared to essential hypertension. To the extent that this defect is associated with an increased platelet aggregability, these data may provide a pathogenetic mechanism for the prevalence of thrombotic events in patients with primary aldosteronism.