Forskolin-stimulated adenylyl cyclase activity is decreased but beta 2-adrenoceptor function is unchanged in primary hypertension

J Cardiovasc Pharmacol. 1993 Nov;22(5):695-701. doi: 10.1097/00005344-199311000-00004.

Abstract

beta 2-Adrenoceptor function may be decreased in primary hypertension, resulting in increased peripheral resistance. To study the beta 2-adrenoceptor function, we used circulating mononuclear leukocytes (MNL) as a model system. Twenty untreated hypertensive subjects [(HT) 10 men and 10 women] and 20 age- and sex-matched healthy normotensive (NT) volunteers were studied. The beta 2-adrenoceptor density was not significantly different between HT and NT, but the dissociation constants for the high- and low-affinity agonist binding states, studied by isoprenaline competition assays, were significantly higher in HT. Stimulation of adenylyl cyclase with isoprenaline (10 microM, beta 2-adrenoceptor-mediated stimulation) was not significantly different between the two groups. Forskolin-mediated direct stimulation of adenylyl cyclase was significantly higher in women than in men. For both sexes, the forskolin-induced cyclic AMP production was lower in the HT group, reaching statistical significance in the men. No major abnormalities were observed in beta 2-adrenoceptor function in mononuclear leukocytes. The putative relation between the decreased forskolin-mediated adenylyl cyclase activity and primary hypertension requires further study.

MeSH terms

  • Adenylyl Cyclases / drug effects*
  • Adenylyl Cyclases / metabolism
  • Adrenergic beta-Antagonists / pharmacology*
  • Adult
  • Binding, Competitive
  • Cell Membrane / drug effects
  • Colforsin / pharmacology*
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Hypertension / drug therapy*
  • Isoproterenol / metabolism
  • Isoproterenol / pharmacology
  • Leukocytes, Mononuclear / drug effects
  • Male
  • Middle Aged
  • Pindolol / analogs & derivatives
  • Pindolol / metabolism
  • Receptors, Adrenergic, beta / drug effects*
  • Sex Factors

Substances

  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, beta
  • Colforsin
  • cyanopindolol
  • Pindolol
  • Adenylyl Cyclases
  • Isoproterenol