In vivo insulin action in genetic models of hypertension

Insulin resistance has been described in nonobese subjects with essential hypertension. At present it is unknown whether hypertension per se may lead to the onset of insulin resistance. To examine this question we studied in vivo insulin action in two rat models of genetic hypertension. Four groups of conscious rats were studied: Milan hypertensive (MHS), Milan normotensive (MNS), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY). Mean arterial pressure was increased in SHR vs. WKY in both the fed (184 ± 5 vs. 126 ± 6 mmHg; P < 0.001) and fasting (160 ± 5 vs. 129 ± 5; P < 0.001) states. During high-dose insulin clamps, total body glucose uptake (mg·kg^{- 1}·min^-1) was similar in MNS (28.7 ± 1.4) vs. MHS (33.6 ± 3.0) and in WKY (34.6 ± 1.8) vs. SHR (35.7 ± 2.4). During low-dose insulin clamps, suppression of hepatic glucose production (3.5 ± 0.6 vs. 3.0 ± 0.5 mg·kg^{- 1}·min^-1) and stimulation of glycolysis (12.9 ± 0.8 vs. 14.4 ± 1.5 mg·kg^-1·min^-1) were similar in WKY vs. SHR, whereas glucose uptake (24.6 ± 1.9 vs. 18.3 ± 1.2 mg·kg^-1·min^-1; P < 0.01) and muscle glycogenic rate (10.2 ± 1.1 vs. 6.5 ± 1.1 mg·kg^-1·min^-1; P < 0.05) were increased in SHR vs. WKY. In conclusion, 1) feeding markedly augments blood pressure in hypertensive but not in normotensive rats, and 2) hepatic and muscle insulin sensitivity are normal or increased in two different rat models of genetic hypertension. These results provide evidence that high blood pressure per se does not invariably lead to the development of insulin resistance.