MICROVASCULAR ADAPTATIONS IN HYPERTENSION

5种实验动物微血管适应性的研究

A survey of microvascular adaptatations in 5 models of experimental hypertension has documented various degrees of vasoconstriction, rarefaction and structural reductions in arteriolar lumen size contributing to increased peripheral resistance. The present proposal will build on this foundation by documenting the restructuring of the microvascular network associated with rarefaction and investigating the mechanisms responsible for microvascular rarefaction. The first experiments will document any network changes that appear in renal hypertension (1KG) and DOCA-salt hypertension of 8 weeks duration. The next studies will test the hypothesis that changes in microvascular density provide a mechanism for long-term autoregulation of blood flow. This will be tested by experiments on the role of the sympathetic nerves, the renin-angiotension system, and by chronic variations in local pressure. Other ramifications of this hypothesis are that rarefaction is a failure of vessels to grow in young animals and that rarefaction is reversible. These ideas will be tested by producing and reversing renal hypertension in adult rats. The third hypothesis is that sodium sensitive individuals have prehypertensive microvascular alterations and this will be tested in Sprague-Dawley rats. Next, the vasoconstriction-volume hypothesis will be tested directly by measurements of vasoconstriction and plasma renin activity in 1KG on either a normal diet or a sodium deficient diet to increase plasma renin levels, and in 2-kidney-1-clip hypertensive rats with benign and malignant hypertension. These hypotheses will be tested in the in situ, transilluminated gracilis muscle of rats anesthetized with chloralose-urethane. Arterial blood pressure will be measured in all terminal experiments through indwelling catheters and in chronic studies by tail cuff. Measurements will be made of microvessel diameters by image-shearing closed circuit television microscopy, and microvessel density by quantitative stereology in vivo and in Microfill preparations. Results of these studies will have implications for human hypertensive disease as well as add to the basic understanding of the microcirculation.