(Hypertension. 1999;34:1134-1140.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Impaired Prostaglandin E2/Prostaglandin I2 Receptor–Gs Protein Interactions in Isolated Renal Resistance Arterioles of Spontaneously Hypertensive Rats
From the Department of Cell and Molecular Physiology (X.R., W.J.A.), University of North Carolina at Chapel Hill; and Inserm Research Unit 489 (C.C.), Tenon Hospital, Paris, France.
Abstract—The protective effect of
vasodilator agents linked to the cAMP pathway is less effective for
buffering the vasoconstrictor effect of angiotensin II in
young animals with genetic hypertension. To determine the underlying
cellular mechanism, experiments were performed on freshly isolated
preglomerular resistance arterioles obtained from kidneys
of 7-week-old spontaneously hypertensive rats (SHR) and normotensive
Wistar-Kyoto rats (WKY). Specific high-affinity saturable binding of
3H-prostaglandin (PG) E2 revealed 1
receptor class in renal microvessels; PGE2 receptor density
was similar in SHR and WKY (106 versus 115 fmol/mg;
P>0.8), as was receptor affinity (3.6 versus 3.5
nmol/L; P>0.7). Basal cAMP activity was similar in
renal arterioles from SHR and WKY. A major finding was that
PGE2, PGI2, and isoproterenol produced weaker
stimulation of cAMP formation in arteriolar cells of SHR
(P<0.02). In contrast, GTP
s and forskolin stimulated
cAMP generation to a similar degree in both rat strains, which suggests
normal adenylate cyclase activity in hypertension-prone
SHR. Immunoblots revealed the presence of 3 classes of G
proteins (Gs, Gi, and Gq) in
preglomerular arterioles. The relative amounts of
discernible G-protein 
-subunits in renal resistance vessels did not
differ between SHR and WKY. These results extend previous in vivo
studies of abnormal renal vascular reactivity in SHR and more directly
localize defective coupling of the prostaglandin and
ß-adrenergic receptors to a stimulatory G protein and cAMP
production in freshly isolated preglomerular
arteriolar cells of young SHR. This dysfunction may be due to an
abnormal interaction between prostaglandin receptors and
Gs protein that leads to inefficient coupling of initiating
steps in the cAMP–protein kinase A cascade during the development
of hypertension.
Key Words: muscle, smooth, vascular • adenyl cyclase • renal circulation • arterioles • vasoconstriction • rats, inbred strains
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