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G protein alterations in hypertension and aging
R D Feldman1, C M Tan, J Chorazyczewski
1Department of Medicine, University of Western Ontario, London, Canada.
Hypertension (Dallas, Tex. : 1979)
|November 1, 1995
Summary
This study investigated guanine nucleotide regulatory proteins (G proteins) in hypertension and aging. Results show impaired G protein function in adenyl cyclase, with distinct changes in stimulatory and inhibitory G proteins in hypertensive and older individuals.
Area of Science:
- Cardiovascular Physiology
- Cellular Signaling
- Molecular Biology
Background:
- Defective vasodilator function is implicated in hypertension, particularly in the elderly.
- Impaired beta-adrenergic vasodilation and reduced lymphocyte beta-adrenergic activation of adenyl cyclase are observed in aging and hypertension.
- The precise cellular mechanisms underlying these alterations are not fully understood.
Purpose of the Study:
- To investigate if defects in guanine nucleotide regulatory proteins (G proteins) contribute to impaired vasodilator function in hypertension and aging.
- To assess alterations in both stimulatory (Gs) and inhibitory (Gi) G proteins linked to adenyl cyclase signaling.
Main Methods:
- Assessed human lymphocyte adenyl cyclase activity.
- Quantified stimulatory G proteins using cholera toxin-mediated [32P]ADP ribosylation and specific antisera.
- Evaluated inhibitory G proteins via pertussis toxin-mediated [32P]ADP ribosylation and specific antisera.
Main Results:
- Lymphocytes from older and hypertensive subjects showed reduced isoproterenol-stimulated adenyl cyclase activity.
- Aluminum fluoride-stimulated activity was reduced only in hypertensive subjects and inversely correlated with mean arterial pressure.
- Hypertensive subjects exhibited increased stimulatory G protein labeling, while older subjects showed increased inhibitory G protein labeling.
Conclusions:
- Alterations in G protein function contribute to impaired adenyl cyclase signaling in hypertension and aging.
- These defects involve divergent changes in stimulatory and inhibitory G proteins, suggesting distinct molecular mechanisms in aging versus hypertension.