title: Platelet alpha2-adrenoceptor alterations in patients with essential hypertension.
abstract: OBJECTIVE
  The purpose of this study was to determine whether human platelet alpha2-adrenoceptors were altered in essential hypertension. A systematic analysis was carried out on 165 normotensives and 124 untreated primary hypertensives.
  
  
  METHODS
  The study was performed at different levels: i) density and affinity of platelet alpha2-adrenoceptors were determined by receptor binding assays using the full alpha2-adrenoceptor agonist [3H]-UK 14304 and a thermodynamic analysis of data was carried out to evaluate if binding mechanisms at the molecular level were altered during hypertension; ii) the functionality of Gi proteins coupled to alpha2-adrenoceptors and iii) forskolin-stimulated cAMP levels were measured.
  
  
  RESULTS
  Platelet alpha2-adrenoceptors mean density (Bmax) and affinity (Kd) (+/-s.e.mean) were significantly lower and higher, respectively, in normotensive than in hypertensive subjects [Bmax=327+/-4 vs 435+/-5 fmol mg(-1) of protein (P<0.01) and Kd=3.76+/-10.05 vs 6.50+/-0.15 nM (P<0.01), respectively]. The 50% stimulating concentration of adrenaline on [35S]-GTPgammaS binding to Gi proteins was significantly (P<0.01) lower in normotensives (12+/-2 nM) than in hypertensives (110+/-10 nM). The 50% inhibiting concentration of adrenaline on forskolin-stimulated cAMP levels was significantly (P<0.01) lower in normotensive (22+/-2 nM) than in hypertensive subjects (200+/-25 nM).
  
  
  CONCLUSIONS
  Present analysis, including receptorial and functional data, provides evidence that marked alterations occur in platelet alpha2-adrenoceptors of hypertensive subjects.
authors: Department of Clinical and Experimental Medicine, University of Ferrara, Italy.
authors: K
authors: K
authors: Varani
authors: S
authors: S
authors: Gessi
authors: A
authors: A
authors: Caiazza
authors: G
authors: G
authors: Rastelli
authors: F
authors: F
authors: Portaluppi
authors: P A
authors: PA
authors: Borea
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics; D001792:Blood Platelets / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011810:Quinoxalines / Q000493:pharmacokinetics*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D000317:Adrenergic alpha-Antagonists; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D005576:Colforsin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000068438:Brimonidine Tartrate; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D004837:Epinephrine