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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Experimental Cardiovascular Sciences Study Section (ECS)
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Eastern Virginia Medical School
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Parker, S B; Dobrian, A D; Wade, S S et al. (2000) AT(1) receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension. Am J Physiol Heart Circ Physiol 278:H613-22
Miriel, V A; Allen, S P; Schriver, S D et al. (1999) Genistein inhibits pressure-induced expression of c-fos in isolated mesenteric arteries. Hypertension 34:132-7
Tulis, D A; Prewitt, R L (1998) Medial and endothelial platelet-derived growth factor A chain expression is regulated by in vivo exposure to elevated flow. J Vasc Res 35:413-20
Parker, S B; Wade, S S; Prewitt, R L (1998) Pressure mediates angiotensin II-induced arterial hypertrophy and PDGF-A expression. Hypertension 32:452-8
Tulis, D A; Unthank, J L; Prewitt, R L (1998) Flow-induced arterial remodeling in rat mesenteric vasculature. Am J Physiol 274:H874-82
Allen, S P; Wade, S S; Prewitt, R L (1997) Myogenic tone attenuates pressure-induced gene expression in isolated small arteries. Hypertension 30:203-8
Allen, S P; Liang, H M; Hill, M A et al. (1996) Elevated pressure stimulates protooncogene expression in isolated mesenteric arteries. Am J Physiol 271:H1517-23
Wang, D H; Prewitt, R L; Beebe, S J (1995) Regulation of PDGF-A: a possible mechanism for angiotensin II-induced vascular growth. Am J Physiol 269:H356-64
Nakamura, T; Granger, J P; Kato, T et al. (1995) Reduced natriuretic response to increased renal interstitial hydrostatic pressure in Dahl salt-sensitive rats during volume expansion. Hypertens Res 18:313-7
Prewitt, R L; Reilly, C K; Wang, D H (1994) Pressure-flow curves reflect arteriolar responses in perfused rat hindquarters. Hypertension 23:223-8

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