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This study investigated the effects of angiotensin II "slow pressor" hypertension on structure and function of nerves supplying the renal vasculature. Low-dose angiotensin II (10 ng/kg per minute, initially sub-pressor) or saline vehicle was infused intravenously for 21 days in rats, and the effects were compared in renal and mesenteric arteries. Mean arterial pressure averaged 12+/-2 mm Hg higher than in vehicle-infused rats at 21 days. Using electron microscopy, the innervation density of renal arcuate, but not mesenteric arteries of equivalent size, was significantly higher in angiotensin II-infused than in vehicle-infused rats. Functional testing on a pressure myograph revealed that constrictions evoked by nerve stimulation in arcuate arteries were 2.3+/-0.7-fold greater in vessels from angiotensin II-infused compared with vehicle-infused rats (P<0.0001), whereas there was no significant difference in nerve-induced constrictions in mesenteric arteries. Sensitivity to and maximum amplitude of constrictions evoked by phenylephrine were not different in renal or mesenteric arteries between groups, suggesting that the increased neurally evoked constriction in renal arcuate arteries was not caused by postsynaptic changes. Endothelium-dependent vasorelaxation and the vessel wall physical properties were not different between the two groups in either artery. Thus, angiotensin II infusion appeared to evoke renal-specific increases in vessel innervation and increased vasoconstriction to nerve stimulation. These changes appear early and occur before changes in renal endothelial function are apparent. Thus, "slow pressor" angiotensin II hypertension is associated with increased renal innervation, compatible with a pathogenetic role.

The effects on the renal vasculature and on arterial blood pressure of chronic infusion of low doses of angiotensin II (Ang II) into the renal artery were studied. Sprague Dawley rats were infused continuously with Ang II (0.5, 1.5, or 4.5 ng. kg(-1). min(-1)) or vehicle into the right renal artery (contralateral nephrectomy). Intrarenal Ang II infusion for 25 days produced dose-dependent rises (P:<0.001) in awake mean arterial pressure (111+/-1, 119+/-5, and 130+/-3 mm Hg in rats receiving 0.5, 1.5, and 4.5 ng. kg(-1). min(-1) Ang II, respectively) compared with 105+/-1 mm Hg (vehicle). Renal vessel lumen characteristics were assessed with an established, maximally dilated, isosmotic perfused kidney preparation. This revealed a small dose-dependent right shift in the pressure-flow relation (P=0.05), as well as a dose-dependent right shift and a dose-dependent reduction in the slope of the pressure-glomerular filtration rate relation (P=0.04 and 0.03, respectively). The effects of Ang II infusion on arterial pressure were not affected by the timing of the contralateral nephrectomy but were reduced when the contralateral kidney remained in situ. Acute losartan administration (10 mg/kg IV bolus) produced similar effects on arterial pressure in rats infused with vehicle or Ang II (4.5 ng. kg(-1). min(-1)) for 14 days, P=0.89), indicating the lack of systemic spillover of Ang II. Intraperitoneal Ang II (0.5, 1.5, or 4.5 ng. kg(-1). min(-1) for 25 days) had no effect on arterial pressure. Thus, chronic intrarenal infusion of low doses of Ang II resulted in changes in the renal vasculature compatible with dose-related structural reductions in the lumen diameter of preglomerular vessels and produced dose-related increases in arterial pressure.

SUMMARY 1. Angiotensin (Ang) II causes growth-related effects on vascular smooth muscle cells in vitro and in vivo. 2. Chronic infusions of AngII systemically, at doses that are initially subpressor, result in slowly progressive increases in arterial pressure (‘slow-pressor’ hypertension). It has been suggested that the hypertension is due to induced growth in systemic resistance vessel walls by the AngII infusions. 3. We report the results of several studies investigating whether there are also induced structural changes in renal resistance vessels during chronic AngII infusions. We have developed models in Sprague-Dawley rats in which low-dose AngII infusions, either into the renal artery (thus restricting the effects to the kidney) or systemically, result in hypertension. 5. In both models, we have evidence suggesting that chronic AngII infusions have resulted in apparent structurally induced reductions in renal vasculature lumen upstream to the glomerulus. 6. The role of these renal changes in the development of the hypertension remain to be determined. [ABSTRACT FROM AUTHOR]