Forskolin-stimulated adenylyl cyclase activity is decreased but beta 2-adrenoceptor function is unchanged in primary hypertension.
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.
Blankesteijn
W M
WM
Department of General Internal Medicine, St. Radboud University Hospital, Nijmegen, The Netherlands.
Willems
P H
PH
Graafsma
S J
SJ
de Pont
J J
JJ
Thien
T
T
D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D001667:Binding, Competitive; D002462:Cell Membrane / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012737:Sex Factors
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; C047975:cyanopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol