Until a few years ago, hypertension was viewed as a disease process which involved a generalized (homogenous) change throughout the arteriolar tree in tissues such as skeletal muscle. Recently, it has been shown that the progression of hypertension is at least a two-step process with initial constriction of the larger arterioles followed by a subsequent constriction of the smaller arterioles. This proposed project will investigate the new and unique concept that the initial constriction of the larger arterioles actually induces the subsequent constriction of the smaller arterioles by modification of oxygen tension in tissues such as skeletal muscle. This project will also study the concept that a change in collagen synthesis at the level of the large arterioles is an important factor both in the maintenance of the large arteriolar constriction and in the modification of oxygen tension to affect the smaller arterioles. If these concepts prove to be true, they will provide a new direction for future studies of arterial wall damage and hypertension therapy. This project will measure oxygen tension at several sites along large (100 to 120 micron diameters) and small (30 to 70 micron) arterioles in skeletal muscle and will evaluate the wall histology of these arterioles. These measurements will be made in rats with a one-kidney one-clip Goldblatt form, a two-kidney one-clip Goldblatt form, and a Deoxycorticosterone-induced form of hypertension to determine if the microvascular oxygen profile and structural changes differ between these models which involve different levels of circulating hormones (renin-angiotensin) during the development of hypertension and during the associated damage to the arteriolar wall. A collagen synthesis inhibitor (Beta-aminopropionitrile) will be given to each hypertensive model to evaluate the role of microvascular collagen deposition on the development of the hypertension and on changes in tissue oxygen tension. It is clearly possible that the initial constriction of large arterioles reduces counter-current oxygen exchange between large arterioles and venules to increase downstream oxygen tension in small arterioles. Elevated oxygen tension could be a primary stimulus for a subsequent constriction of the smallest arterioles to further increase peripheral resistance and to increase intraluminal pressure in the upstream large arterioles. This increased pressure (as well as elevated oxygen tension) could accelerate collagen synthesis because of damage to the arteriolar wall.