Mechanisms of protection against stroke in stroke-prone spontaneously hypertensive rats

Abstract

The purpose of this study was to examine mechanisms by which sympathetic nerves protect against cerebral hemorrhage and ischemic infarction (i.e., "stroke") in stroke-prone spontaneously hypertensive rats (SHRSP). When unilateral superior cervical ganglionectomy was performed in SHRSP at 1 mo of age, development of cerebral vascular hypertrophy was inhibited and stroke developed only in the denervated hemisphere in 79% of the rats (P less than 0.05). Because "trophic" effects of sympathetic nerves on vascular growth may be less in older animals, unilateral sympathetic denervation was performed in SHRSP at 3 mo of age. The incidence of stroke was similar in the innervated and denervated hemispheres. In another group of rats that had unilateral ganglionectomy at 1 mo, we examined regulation of cerebral blood flow (CBF) when the rats were 4-5 mo of age, before neurologic signs of stroke. CBF, measured with microspheres, was similar in the innervated and denervated hemispheres during control conditions and during maximal vasodilatation produced by bicuculline. In contrast, when mean arterial pressure was raised acutely, CBF increased more in the denervated hemisphere than in the innervated hemisphere. We conclude that 1) in contrast to effects of denervation at 1 mo, sympathetic denervation at 3 mo of age (when trophic effects are less) does not lead to stroke, and 2) chronic denervation impairs the cerebral vasoconstrictor response to acute increases in arterial pressure.