EFFECT OF SYMPATHETIC DENERVATION ON THE RELAXING RESPONSES OF RABBIT ARTERIAL SMOOTH-MUSCLE

1 The present study reports on the influence of chemical denervation by 6-hydroxydopamine (6-OHDA) on the relaxing responses to carbachol, sodium nitroprusside, zaprinast, adenosine, forskolin and 3-isobutyl-1-methylxanthine (IBMX) of ring preparations of rabbit renal and femoral arteries. 2 Carbachol was found to induce a complete abolition of the tone induced by 5-hydroxytryptamine (0.1-1.0 mu M), both in the renal and the femoral arteries. The profile of the carbachol-induced relaxation in both the renal and femoral arteries obtained from 6-OHDA-treated rabbits was similar to that observed in control animals; relaxing responses obtained with some of the concentrations of carbachol were, however, found to be greater (P<0.01) in denervated arteries. Sodium nitroprusside was also found to be an effective relaxant agent in both renal and femoral arteries, though more potent in the former but was unaffected by denervation. Zaprinast relaxed both renal and femoral artery ring preparations, and again, no significant difference was observed between control and denervated animals. 3 The cyclic AMP-mediated relaxing responses to adenosine, forskolin and IBMX were found to be similar in renal and femoral arteries of control arteries, producing almost complete abolition of pre-existing tone. The adenosine- and IBMX-induced relaxing responses in renal and femoral arteries were found to be similar in control and denervated animals. However, the concentration-response curve to forskolin was shifted to the left by 2.5 and 1.5 log units in preparations of renal and femoral arteries of denervated rabbits, respectively. 4 The results presented here suggest that: (1) the basal production of cyclic GMP does not appear to be different in the two arteries, but differences in the generation of EDRF or in the activity of guanylate cyclase appear to exist; (2) the basal production of cyclic AMP is of about the same magnitude in the two arteries, and the same applies to adenylate cyclase activity, and finally, (3) sympathetic denervation increases the responses of arterial smooth muscle to activation of adenylate cyclase by forskolin, but not by adenosine.