Increased insulin sensitivity in the high sodium one-kidney, one figure-8 hypertensive rat

Abstract

This study examines the relation between sympathetic activity and in vivo insulin-mediated glucose metabolism in a rat model of acquired hypertension. Two groups of conscious, unrestrained rats were studied in the postabsorptive state: sham-operated normotensive rats (n = 10) and renal-wrapped hypertensive rats (n = 10). Mean arterial pressure was increased in the hypertensive compared with the normotensive group in the fed (184±9 versus 144±6 mm Hg;p<0.01) and in the fasting (147±8 versus 112±7 mm Hg; p<0.01) state. After a 24-hour fast, hepatic glucose production, plasma glucose, insulin, and norepinephrine concentrations were similar in the two groups. Blood pressure did not change in either group during the 3-milliunits/kg · min euglycemic insulin clamp study; however, plasma norepinephrine concentration rose significantly in hypertensive (207±24 versus 329±11 pg/ml; p<0.05) but not in normotensive rats (229±23 versus 267±27 pg/ml; p=NS). During the insulin clamp study, the hepatic glucose production was similar in the hypertensive (3.8±0.8 mg/kg · min) compared with the normotensive (4.0±0.3 mg/kg · min) rats. Insulin-mediated glucose uptake was significantly higher in hypertensive than in normotensive rats (33.0±0.7 versus 25.8±0.8; p<0.01). This increase was mostly due to a marked increase in skeletal muscle glycogen synthesis in the hypertensive versus the normotensive group (11.9±1.0 versus 6.9±0.8; p<0.01), whereas the stimulation of whole body glycolysis (production Of 3H2O) was not significantly different in the two groups (14.7±0.8 versus 15.9±0.9 mg/kg · min in normotensive and hypertensive rats, respectively; p=NS). After euglycemic insulin infusion, plasma norepinephrine concentration increased in hypertensive but not in normotensive rats; however, the blood pressure did not change in either group. Peripheral insulin sensitivity is increased in rats with acquired sodium-sensitive hypertension. These results indicate that sodium-dependent hypertension is associated with enhanced response of the sympathetic nervous system to insulin and with increased insulin sensitivity.