RENAL MICROVASCULATURE IN HYPERTENSION

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The kidneys play a major role in blood pressure regulation. There is an alteration of renal vascular parameters (renal blood flow and renal vascular resistance) early in essential hypertension as well as in the spontaneously hypertensive rat (SHR), a genetic rat model of hypertension. Renal vascular alterations can affect renal function because vascular and tubular functions are intricately linked through auto-regulatory mechanisms. Therefore, the renal vascular alterations may contribute to the development and maintenance of the elevated blood pressure. The proposed project will examine the renal afferent arteriole (the major resistance vessel in the kidney) in a genetic rat model of hypertension (the Okamoto SHR) from birth through 18 weeks to ascertain the role of the renal microvasculature in the development of hypertension. Afferent arteriolar diameters will be determined in renal vascular casts, studied by scanning electron microscopy in SHR, WKY (Wistar Kyoto) and Wistar rats. Diameter measurements will be made in animals with and without maximal vasodilation. The vasodilation will allow an assessment of relative contributions of extrinsic (vasoconstriction) and intrinsic (vascular structure) factors in the renal vascular differences in hypertension. Smooth muscle cells of renal afferent arterioles will be examined by scanning and transmission electron microscopy. Morphometric methods will be used to analyze whole cell size and cytologic features of the smooth muscle cells in hypertensive and normotensive rat strains at ages from newborn to 18 weeks. Structural differences and/or changes associated with the development and maintenance of hypertension will be identified. This project will provide information on the relationship between the renal microvasculature and the development of hypertension as well as a comprehensive examination of vascular smooth muscle cell differentiation in normotensive and hypertensive animals. These data will provide insight into vascular aspects of the pathogenesis of hypertension and associated vascular changes. The long term objectives of the project are (1) to determine the relationship of the renal microvasculature to blood pressure regulation and hypertension, (2) to understand the ontogenesis of vascular smooth muscle cells and alteration which may relate to the pathogenesis of hypertension and (3) to understand what regulates smooth muscle cell differentiation in the kidney, both normal and abnormal.