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

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.

• Authors: W M Blankesteijn, P H Willems, S J Graafsma, J J de Pont, T Thien
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 22 Issue 5 Pg. 695-701 (Nov 1993) ISSN: 0160-2446 [Print] United States
• PMID: 7506320 (Publication Type: Journal Article)

Chemical References

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

Topics

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