Modulation of norepinephrine release in sympathetic nerve endings in renal hypertensive dogs

Experimental renal hypertensive and normal dogs with femoral arteries constantly perfused were studied. Cocaine was used to block the presynaptic norepinephrine (NE) reuptake and tyramine to initiate the release of NE in sympathetic nerve endings. NE spillover and infusion pressure were measured under basic conditions and during intraarterial infusion of cocaine, tyramine and in combination with alpha 1 and alpha 2 adrenoceptor antagonists. The extent of NE spillover increase induced by infusion of tyramine, the increased infusion pressure by cocaine and tyramine, and the reduced infusion pressure by prazosin were all greater in hypertensive dogs than those in normal dogs, but adrenoceptor antagonist idazoxan further increased tyramine-induced NE spillover in normal dogs only. It was suggested that reduced-regulation of presynaptic alpha 2 adrenoceptors to NE release and increased responsiveness of postsynaptic alpha 1 adrenoceptors to NE were present in hypertensive dogs.