This proposal will evaluate mechanisms which influence the local regulation of major resistance arterioles, the long term processes by which large through small arterioles of the intestine are formed and altered during juvenile development and the consequences of hypertension in development of the microvascular branching pattern. Major resistance vessels may be influenced by events which occur in and around the paired venule and are transmitted to the accompanying arteriole. Pilot studies indicate that reduction in venular wall PO2 caused arteriolar vasodilation while elevation of venular wall PO2 caused arteriolar constriction. While changes in venular wall PO2 may directly alter arteriolar wall PO2 and this possibility will be studied, a change in venular wall PO2 may also activate local neural reflexes or cause the release of vasoactive compounds. Pilot studies indicate Endothelial Derived Relaxing Factor (EDRF) can be released from venules and cause arteriolar dilation and the vasodilation upon reduced venular PO2 is greatly attenuated by EDRF blocking agents. A form of regulation of major arterioles unique to the intestine is the increase in tissue hyperosmolarity caused during intestinal absorption. Whether submucosal hyperosmolarity is primarily caused by venous blood from the mucosa or lymph flow from villus lacteals will be determined. Thereafter, the relative role of tissue hyperosmolarity in absorptive hyperemia will be ascertained by comparison of arteriolar dilation during absorption and at comparable elevations of tissue osmolarity at rest caused by hyperosmotic perfusion of the lymphatic system. During juvenile development particularly after 10 weeks in rats, branches of large through small arterioles are formed by an as yet unknown process. A technique which allows observation of the same set of intestinal vessels from branching development proceeds. Available data indicates the branching development in hypertensive rats is suppressed by 20-30% by adult life even though normal vascular density exists at age 4 weeks. The studies will determine at what stage of hypertension the suppression of vascular branching development occurs and if prevention of hypertension can restore normal branching development.
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