Effect of neonatal sympathectomy on development of angiotensin II-induced hypertension.

We tested, in the early stage of angiotensin II (ANG II)-induced hypertension, whether sympathectomy prevented the autopotentiation of vasoconstrictor responses by ANG II and, in the chronic, established phase of hypertension, whether the antihypertensive effect of sympathectomy, if any, was related to the prevention of structural vascular changes. Neonatally and sham-sympathectomized male Sprague-Dawley rats received 100 or 200 ng x kg(-1) x min(-1) ANG II intraperitoneally for 7-10 days or 200 ng x kg(-1) x min(-1) ANG II subcutaneously for 4 wk. Sham-treated sympathectomized and sham-sympathectomized rats were controls. Vasoconstrictor responses to ANG II, norepinephrine (NE), arginine vasopressin, and periarterial nerve stimulation were measured in the mesentery of rats, and thereafter, in the chronically treated rats, mesenteric resistance arteries were fixed in situ for morphometric measurements. In ANG II-treated sham-sympathectomized rats: 1) tail systolic blood pressure was unchanged after 7-10 days and increased by 23 mmHg at 4 wk (P < 0.001); 2) vasoconstrictor responses were selectively increased to ANG II (autopotentiation; P = 0.026) and nerve stimulation (P = 0.031) at 7-10 days and nonselectively increased to all stimuli at 4 wk (P < 0.05 to P < 0.01); and 3) after 4 wk, the wall-to-lumen ratio of resistance arteries was increased (P < 0.02). In ANG II-treated sympathectomized rats, there were no changes in systolic blood pressure or vasoconstrictor responses at either 7-10 days or 4 wk, but structural vascular changes developed to the same extent as in sham-sympathectomized ANG II-treated rats. Autopotentiation of vasoconstrictor responses appears to be due to an interaction between ANG II and the sympathetic nervous system, because it is prevented by sympathectomy. The dissociation of function and structure in the chronic stage of ANG II administration to sympathectomized rats suggests that structural vascular changes by themselves are insufficient to cause hypertension, but increased vascular reactivity or vasoconstrictor input is also needed.