STRUCTURE AND FUNCTION OF CNS VESSELS IN HYPERTENSION

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The cerebrovascular system adapts to chronic hypertension primarily by development of hypertorophy of the media (smooth muscle) in the precapillary resistance vessels and by alteration of the pattern, density, and activity of the sympathetic innervation in large arteries. We propose to examine the hypothesis that these structural adaptations in large and small vessels in chronic hypertension are conducive to normal find morphology and function of downstream cerebral microvessels. The local microvascular supply within nuclei, tracts and layers of selected structures in the brains of hypertensive animals have not yet been evaluated with sensitive methods. Specific objectives of this proposal are to determine 1) the effects of chronic hypertension on the wall structure and sympathetic innervation across all consecutive vascular segments in the brain using light and electron morphometry, 2) the rate of capillary blood flow, blood-brain exchange of small labeled solutes with different physicochemical properties (ethylene glycol, sucrose, urea), and microvascular plasma space in specific selected structures of normotensive and hypertensive animals using quantitative autoradiography, and 3) correlate the structural and physiological information at the local level. We will use six month old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). The morphometric studies of large and small vessels will include measurements of idameters and lengths, and the thickness of smooth muscle layers. We will quantitatively describe at the light and electron microscopic levels nerve-smooth muscle relationships and the fine structure of endothelial cells for all vascular segments. These findings will be correlated, within individual structures where possible, to the physiological information obtained by quantitative autoradiography. All of these determinations will be made in WKY and SHR with intact sympathetic innervation and with unilateral sympathetic denervation (removal of one superiod cervial ganglion at one month of age). To further examine cerebrovascular morphology and function in intact and unilaterally-denervation rats under different conditions, we will repeat these measurements in rats in which we 1) produce acuts arterial hypetension, and 2) electrically stimulate the substantia nigra, a procedure causing highly focal metabolic activation of basal ganglia within the field of nigral projections. Respectively, these two manipulations allow evaluation of the ability of the cerebrovascular system in chronic hypertension to respond to mechanical and local metabolic stimuli.