The purpose of these proposed studies is to examine directly the responses of intraparenchymal cerebral arterioles under various pathological and physiological conditions, and to compare these responses to the responses of pial arterioles. Arteriolar diameter will be determined using two different methods: 1) the diameter of pial arterioles will be measured in vivo, and 2) wall-to-lumen ratio of parenchymal and pial arterioles will be determined in cerebral tissue rapidly frozen with supercooled isopentane. These studies will be performed primarily in rats. The first specific aim will be to determine the response of parenchymal arterioles to increases in blood pressure beyond the autoregulatory range of cerebral blood flow, and to determine whether changes in arteriolar caliber are related to disruption of the blood-brain barrier. Acute hypertension will be produced with occlusion of the thoracic aorta, and the degree of barrier disruption will be determined with ultrastructural quantitation of pinocytosis in arteriolar endothelium. The second specific aim will be to determine the effects of chronic hypertension on dilator and constrictor responses of cerebral arterioles, and to determine whether prevention of vascular hypertrophy normalizes arteriolar responses. In these studies, the responses of innervated and denervated cerebral arterioles in stroke-prone spontaneously hypertensive rats will be compared during hypercapnia and during increases in blood pressure. Sympathetic denervation prevents cerebral vascular hypertrophy in these rats. The third specific aim will be to compare the responses of parenchymal and pial arterioles during autoregulation. Blood pressure will be reduced with controlled hemorrhage and increased with aortic obstruction. The fourth specific aim will be to compare the responses of parenchymal and pial arterioles to altered cerebral metabolism. The response of cerebral arterioles to bicuculline-induced seizure will be compared with the response to hypercapnia. The fifth specific aim will be to determine the response of parenchymal arterioles to sympathetic stimulation. The cervical sympathetic trunk will be stimulated unilaterally in cats. The studies will provide valuable information relevant to hypertensive encephalopathy, the cerebral vascular complications of chronic hypertension, and to the regulation of cerebral vascular resistance. Although performed in animals, these studies will be applicable to human disease.
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