Diabetes results in profound metabolic disturbances, and the extent to which hypertension may cause further deterioration of these functions is not clear. Relatively few metabolic functions have been studied in hypertensive animals, and fewer still in diabetic hypertensives. This investigation will examine changes in key regulatory enzymes in normotensive and hypertensive rats, and in diabetic and hypertensive diabetic animals. Enzymes that regulate the pathways of lipogenesis, glycolysis, gluconeogenesis, ammoniagenesis, ureagenesis, and nucleotide synthesis will be measured in heart, kidney and liver. Since many adaptive enzymes respond to dietary changes, measurements will be made in fed and in 48 hour-fasted animals. During the period of the proposal, three models of hypertension will be examined, including a genetic model (the spontaneously hypertensive rat), including the Goldblatt model where hypertension is induced by clipping the renal artery, and the DOCA-salt model wher hypertension is induced by giving sodium chloride and a mineralocortcoid. Diabetes will be induced with streptozotocin after the development of hypertension as monitored by cannulation of the femoral artery. Presence of diabetes will be ascertained by showing that urinary glucose exceeds 1%; in some cases, plasma glucose will also be measured. Tissue glycogen content will be determined for each group. These measurements will test the ideas that secretion or response of tissues to catecholamines or other hormones is altered by hypertension, and that presence of high blood pressure modifier the normal metabolic response to diabetes.
