Short-term aortic barodenervation diminishes α 1-adrenoceptor reactivity in rat aortic smooth muscle

Abstract

Our previous studies have shown that aortic baroreceptor denervation elicits acute increases in blood pressure and significant elevations of sympathetic activity and peripheral vascular resistance. This study investigated the short-term (3 and 48 h) effect of aortic barodenervation and associated sympathetic hyperactivity on the functional activity of α 1-adrenoceptors in rat aortic smooth muscle. Compared with sham operation, aortic barodenervation caused acute rises in blood pressure and heart rate and reductions in baroreflex sensitivity. Blood pressure and heart rate remained elevated when measured in conscious aortic barodenervated rats 3 h after surgery but subsided to sham-operated levels at 48 h; the baroreflex sensitivity, however, remained attenuated. Hexamethonium (0.5–4 mg/kg, i.v.) elicited significantly ( P<0.05) greater depressor responses in conscious aortic barodenervated rats than in sham-operated rats at both 3 and 48 h, suggesting a higher sympathetic activity in denervated rats. Exposure of aortic rings from aortic barodenervated and sham-operated rats to cumulative addition of phenylephrine (α 1-adrenoceptor agonist, 3×10 −8–1×10 −4 M) resulted in concentration-related contractile responses that were similar in the two groups of rats at 3 h in contrast to significantly ( P<0.05) smaller contractions in rings from denervated rats at 48 h. The maximum contraction developed ( E max) at 48 h showed approximately 50% reduction in rings from aortic barodenervated compared with sham-operated rats (239±16 vs. 558±15 mg tension/mg tissue). The pA 2 value for prazosin (α 1-adrenoceptor antagonist) was not altered by aortic barodenervation at 3 h but showed significant ( P<0.05) increases, compared with sham-operated values, at 48 h. It is concluded that short-term aortic barodenervation results in an elevation of sympathetic activity that coincides with reduced responsiveness of aortic smooth muscle to α 1-adrenoceptor activation. The aortic barodenervation-induced α 1-adrenoceptor desensitization is not a result of decreased receptor affinity but may involve an alteration of receptor density or in the post-receptor activation events. © 1997 Elsevier Science B.V. All rights reserved.