Platelet alpha(2)-adrenoceptor alterations in patients with essential hypertension

Aims The purpose of this study was to determine whether human platelet alph a(2)-adrenoceptors were altered in essential hypertension. A systematic ana lysis was carried out on 165 normotensives and 124 untreated primary hypert ensives. Methods The study was performed at different levels: i) density and affinit y of platelet alpha(2)-adrenoceptors were determined by receptor binding as says using the full alpha(2)-adrenoceptor agonist [H-3]-UK 14304 and a ther modynamic analysis of data was carried out to evaluate if binding mechanism s at the molecular level were altered during hypertension; ii) the function ality of G(i) proteins coupled to alpha(2)-adrenoceptors and iii) forskolin -stimulated cAMP levels were measured. Results Platelet alpha(2)-adrenoceptors mean density (B-max) and affinity ( K-d) (+/-s.e.mean) were significantly lower and higher, respectively, in no rmotensive than in hypertensive subjects [B-max=327+/-4 vs 435+/-5 fmol mg( -1) of protein (P<0.01) and K-d=3.76+/-0.05 vs 6.50+/-0.15 nM (P<0.01), res pectively]. The 50% stimulating concentration of adrenaline on [S-35]-GTP g amma S binding to G(i) proteins was significantly (P<0.01) lower in normote nsives (12+/-2 nM) than in hypertensives (110+/-10 nM). The 50% inhibiting concentration of adrenaline on forskolin-stimulated cAMP levels was signifi cantly (P<0.01) lower in normotensive (22+/-2 nM) than in hypertensive subj ects (200+/-25 nM). Conclusions Present analysis, including receptorial and functional data, pr ovides evidence that marked alterations occur in platelet alpha(2)-adrenoce ptors of hypertensive subjects.