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(Hypertension. 1999;34:1134-1140.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Impaired Prostaglandin E₂/Prostaglandin I₂ Receptor–G_s Protein Interactions in Isolated Renal Resistance Arterioles of Spontaneously Hypertensive Rats

Xiaoping Ruan; Christos Chatziantoniou; William J. Arendshorst

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, GTPs 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 (G_s, G_i, and G_q) 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 G_s 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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