Upper limit of cerebral autoregulation during development of hypertension in spontaneously hypertensive rats — effect of sympathetic denervation

Abstract

The upper limit of cerebral autoregulation was studied in pre- or early established hypertension in spontaneously hypertensive rats (SHR). Cerebral blood flow (CBF) was measured with the hydrogen clearance method, and wall/lumen ratio of cerebral arteries was morphometrically measured with the freeze-substitution technique. To test autoregulation, phenylephrine was intravenously infused to cause stepwise increments of blood pressure. Unilateral superior cervical ganglionectomy was carried out to examine the effects of sympathetic denervation on CBF autoregulation and thickness of vascular wall. Resting blood pressure at 4 weeks, 3 months and 6 months of age were 89 ± 3 mm Hg (mean ± SEM), 140 ± 6 and 165 ± 6, respectively. Baseline CBF was slightly diminished with age; 50.6 ± 9.2 ml/100 g/min at 4 weeks, 49.8 ± 8.1 at 3 months and 44.1 ± 5.6 at 6 months. The upper limit of autoregulation was markedly raised with age; 118 ±5 mm Hg at 4 weeks, 180 ± 7 at 3 months and 208 ± 10 at 6 months. Acute sympathetic denervation lowered the upper limits to 105 ± 2, 162 ± 4 and 185 ± 7 mm Hg, respectively. On the other hand, in chronic denervation which was made at 4 weeks of age, the upper limit of autoregulation in the denervated hemisphere was slightly lower than that in innervated hemisphere at 2 months (165 ± 5 and 178 ± 6 mm Hg), and at 5 months (202 ± 8 and 215 ± 8 mm Hg) after ganglionectomy. Wall to lumen ratio was increased with the elevation of basal blood pressure; 0.131 ± 0.008 at 4 weeks, 0.170 ± 0.005 at 3 months and 0.223 ± 0.007 at 6 months. Chronic denervation reduced such increased ratio to 0.128 ± 0.004 at 2 months and 0.196 ± 0.007 at 5 months after ganglionectomy. We conclude that during development of hypertension, the upward shift of CBF autoregulation is closely related to an elevation of basal blood pressure, which is also correlated to the thickness of vessel wall. By means of tonic and trophic effects, sympathetic innervation appears to play an important role in regulation of CBF in response to acute elevations of systemic blood pressure. © 1985 American Heart Association, Inc.