AJP - Regulatory, Integrative and Comparative Physiology, Vol 265, Issue 4 798-R803, Copyright © 1993 by American Physiological Society
Decreased potency of contraction to alpha-adrenoceptor stimulation in renal arteries from obese hypertensive dogs
P. H. Ratz, D. B. West and J. P. Granger
Department of Pharmacology, Eastern Virginia Medical School, Norfolk 23501.
The contractile potencies of the alpha-adrenoceptor agonist phenylephrine
(PhE) and two nonadrenergic vasoconstrictors, prostaglandin F2 alpha (PGF2
alpha) and endothelin, were evaluated in renal arterial muscle strips
isolated from obese hypertensive (OH) dogs. Responses were compared with
those obtained from renal arteries isolated from lean normotensive (LN)
dogs. Identical dose-response curves were produced by PGF2 alpha in
arteries from OH and LN dogs. This was also true for endothelin. However,
the vasoconstrictor potency of PhE for arteries from OH dogs was
approximately 2.5-fold less than that for arteries from LN dogs. This
difference was not dependent on endothelial integrity. Although they were
less potent to PhE, arteries from OH dogs did not produce weaker maximum
contractile responses than arteries from LN dogs; responses produced by
maximum K+ depolarization (S(o)) were approximately 2 x 10(5) N/m2, and
responses to the maximally effective concentrations of PhE, PGF2 alpha, and
endothelin were approximately 0.97-, 0.50-, and 0.87-fold S(o),
respectively. In addition to the rightward shift in contractile potency to
PhE, arteries from OH dogs precontracted with a maximum PhE concentration
relaxed more to a high nitroglycerin concentration than did arteries from
LN dogs. At a PhE concentration that produced equivalent maximum force
responses, arteries from OH dogs had a lower rate of muscle shortening than
did arteries from LN dogs, suggesting reduced cross-bridge activation in
the arteries from OH dogs. These data suggest that
alpha-adrenoceptor-induced activation was selectively downregulated in
renal arteries from OH dogs.
