Blood flow to the brain is relatively constant over a wide physiological range of systemic pressures. The control for this cerebrovascular autoregulatory behavior is believed to involve the smooth muscle cells of pre-capillary arterioles and small arteries. In chronic hypertension, the limits of autoregulation are alterted. Our previous studies have shown that isolated, intact segments of 80-200Mum (ID) brain arteries from the rat exhibit spontaneous tone and rhythmicity, graded cellular membrane depolarization with increasing transmural pressure and myogenicity and forced dilatation. We plan to quantify these cellular and myogenic properties in brain arteries by a variety of unique techniques to better establish a pathophysiologic basis for the cerebrovascular changes brought about by chronic hypertension. We will use middle cerebal artery branches from the stroke-prone spontaneously hypertensive rat (SHRSP) and the anti-hypertensive treated SHRSP. Mechanical data will be obtained from microscopic, video-determined dimensions of cannulated 100-200Mum resistance arteries subjected to constant and pulsatile pressures and various flow conditions. Specifically, we will characterize pressure-diameter, tension-circumferential length, smooth muscle cell stress-strain, spontaneous activity and tone, and sausage-string and force vasodilatation phenomena. In many experiments, simultaneous electrophysiologic methods will be used to establish transmembrane and action potentials coincident with these various vessel states. Vessels will be fixed for wall morphology, and tests will be conducted to determine the influence of neurotransmitter release, pH, Ca concentration and contractile agonists. This study is aimed at the blood flow regulatory mechanisms operative in a single resistance artery under manipulative and controlled in vitro conditions. We will examine the validity of the series tension hypothesis of myogenicity, and seek other plausible schemes. The results will provide new information about the relation of vascular myogenicity to autoregulation and to the membrane and vessel wall changes induced by hypertension. This study will add to our understanding of intrinsic events within the vessel wall itself which can result in hypertension-induced blood brain barrier breakdown, stroke and encephalopathy.
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