Deficient activity of stimulatory nucleotide-binding regulatory protein in lymphocytes from patients with essential hypertension.
Lymphocytes are widely used as a model for the cardiovascular beta-adrenoceptor-adenylate cyclase system. We evaluated the role of this system in the pathogenesis of hypertension by studying lymphocytes obtained from patients with essential hypertension. Untreated hypertensive patients and normotensive control subjects were studied. The number and affinity of the beta-adrenoceptors were measured by a radioligand binding method with 125I-cyanopindolol. The responses of cyclic adenosine monophosphate (cAMP) to isoproterenol, cholera toxin, and forskolin were also determined. The concentration and affinity of beta-adrenoceptors did not differ significantly in the two groups, nor was a significant difference found in the basal level of cAMP. The effects of isoproterenol on the accumulation of cAMP were reduced in the lymphocytes from the hypertensive compared with the normotensive subjects. There was no significant difference in the effect of forskolin on cAMP accumulation in the two groups. These results indicate that the activity of the stimulatory nucleotide binding regulatory protein (Gs-protein) is reduced in lymphocytes from patients with essential hypertension. This defect of Gs-protein in the lymphocytes may represent a defect of Gs-protein in the cardiovascular system in such patients.
Yoshikawa
H
H
Department of Medicine, Wakayama Medical College, Japan.
Fukuda
K
K
Wanaka
Y
Y
Kasamatsu
K
K
Baba
A
A
Nishio
I
I
Masuyama
Y
Y
D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood*; D007545:Isoproterenol / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol