(Hypertension. 1995;26:725.)
© 1995 American Heart Association, Inc.
Articles |
G Protein Alterations in Hypertension and Aging
From the Departments of Medicine and Pharmacology and Toxicology, University of Western Ontario, London, Ontario, Canada.
Correspondence to Dr R.D. Feldman, 6-L13 University Hospital, PO Box 5339, 339 Windermere Rd, London, Ontario, Canada N6A 5A5.
Abstract Defective vasodilator function could be important in
the pathogenesis and/or maintenance of the hypertensive state
and the predisposition of the elderly to hypertension. Impaired
ß-adrenergic–mediated vasodilation and reduced lymphocyte
ß-adrenergic activation of adenyl cyclase have been demonstrated
both in aging and with hypertension. The cellular mechanisms
responsible for these alterations remain unclear. To determine if these
defects may be due to alterations in guanine nucleotide
regulatory proteins (G proteins) that link receptor activation with
effector function, we assessed (1) human lymphocyte adenyl cyclase
activity, (2) stimulatory G proteins by cholera toxin–mediated
[32P]ADP ribosylation and, in hypertensive subjects, with
s-specific and ß-subunit antisera, and (3)
inhibitory G proteins by pertussis toxin–mediated
[32P]ADP ribosylation and, in older subjects, with
i1,2- and ß-subunit–specific
antisera. Lymphocytes from older subjects and from hypertensive
subjects demonstrated a comparable reduction in
isoproterenol-stimulated adenyl cyclase. However, aluminum
fluoride–stimulated activity was reduced only in
lymphocytes from hypertensive subjects. Furthermore, aluminum
fluoride–stimulated activity was inversely correlated with
mean arterial pressure. In lymphocytes from younger
hypertensive subjects, cholera toxin–mediated labeling was
significantly reduced; however, stimulatory G protein labeling by
immunodetection was unaltered. In lymphocytes from older subjects,
cholera toxin–mediated labeling was not altered; however,
pertussis toxin–mediated labeling was significantly increased. In
contrast, inhibitory G protein labeling by immunodetection
was unaltered. Overall, the study suggests alterations of G protein
function in hypertension and aging. In both conditions, stimulation of
adenyl cyclase is impaired. However, these defects are associated with
divergent alterations in stimulatory and inhibitory G
proteins.
Key Words: G proteins • adenyl cyclase • hypertension
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