Although it is well documented that hypertension alters the microcirculation resulting in chronic elevation of peripheral resistance, no clear picture of the microvascular events which underlie the development of the increased resistance has emerged. The overall purpose of this proposal is to identify and understand the segmental and temporal microvascular alterations which occur during the development of renal hypertension. A secondary goal of this proposal is to understand whether large arteries are regulated sites of resistance and how their activity is coordinated with other series-coupled arterial vessels. To achieve the primary goal of this proposal, studies will be performed on two-kidney, onc-clip renovascular hypertensive rats at 2, 4, and 8 weeks after stenosis of the renal artery. A combination of macro- and microcirculatory techniques will be used in these studies. This will permit whole organ hemodynamic alterations to be understood in terms of the changes occurring in individual microvessels. In these studies, the microvascular changes in resistance will be partitioned into neural, humoral, autoregulatory and structural components in order to understand the relationship between primary causative and secondary compensatory vascular reactions. To achieve the secondary goal of this research program, a network analysis approach will be applied to the microcirculation which permits the network resistance to be partitioned into a compartment containing primarily microvessels and a compartment containing macrovessels (larger arterioles). Using this approach, the ability of large arterioles to act as sites for controlling resistance and flow will be studied and quantitated during the application of vasodilators, during reactive hyperemia and during functional hyperemia. It is hoped that the products of this research proposal will include 1) an understanding of the microvascular changes and mechanisms which underlie chronically elevated peripheral resistance in hypertension and 2) an improved understanding of the arterial sites which can exert control over resistance and tissue flow. In summary, by improving our basic understanding of vascular mechanisms in hypertension and in local control of blood flow, this proposal should provide information valuable for improving diagnosis and for designing new treatment regimes.
