Impaired vasodilator function in hypertension: the role of alterations in receptor-G protein coupling.
Defects in vascular relaxation mechanisms may have an important role in the pathogenesis and maintenance of the elevation in peripheral vascular resistance characteristic of the hypertensive state. Receptor systems that mediate vasorelaxation via elevation of vascular smooth muscle intracellular cAMP concentrations appear to be globally impaired. Recent studies have indicated that this defect may be due to alterations in the transmembrane signaling processes that link receptor activation with the stimulation of adenylyl cyclase. Reduced G-protein function has been reported. However, increased activity of a member of a family of enzymes, the G protein-receptor kinases (GRK), which reduces the efficiency of coupling between the receptor and G protein, may be the key factor accounting for impaired receptor-mediated adenylyl cyclase activation and impaired vasodilator function in the hypertensive state.
Feldman
R D
RD
London Health Sciences Center, London, Ontario, Canada.
Gros
R
R