Glucose metabolism and insulin sensitivity in Dahl hypertensive rats

There is increasing recognition that hypertension is only one facet of a metabolic syndrome that represents a cluster of risk factors including insulin resistance evident during long-term development of cardiovascular disease. The objectives of the present study were to evaluate glucose metabolism and insulin sensitivity in the Dahl genetic salt-sensitive rat model of hypertension and to find out whether there is a correlation between high blood pressure, salt sensitivity and insulin sensitivity. The experiments were performed in Wistar and Dahl salt-resistant (DSR) and salt-sensitive (DSS) rats given a normal or salt-loaded (2% NaCl in the drinking water) diet for 2 months. Glucose turnover, metabolic clearance of glucose and insulin sensitivity were determined using the euglycemic clamp technique in anesthetized animals. Four different concentrations of insulin were used (2.1, 4.2, 8.4 and 16.8 mg/kg/min) with results showing that there were no significant differences in serum glucose and insulin levels, glucose utilization and clearance and insulin sensitivity between Wistar and DSR; these groups remained normotensive throughout the 2-month experiment. However, DSS rats, even on a normal diet, developed hypertension by the end of the experiment and consistent with their hypertensive condition, significantly decreased glucose utilization and clearance and decreased insulin sensitivity were observed. The changes were more marked at higher insulin infusion rates (8.4 and 16.8 mg/kg/min). These results demonstrate that DSS rats with fully developed hypertension were insulin resistant. In contrast, DSR rats remained normotensive despite sodium loading. Sodium loading significantly exaggerated the hypertensive state of DSS rats but did not further increase insulin resistance. The results from respective weanling rats showed that even at this early stage before development of hypertension, DSS rats already had significantly increased serum insulin suggesting insulin resistance. In conclusion, the present results suggest that DSR genetically hypertensive rats were insulin resistant although insulin resistance was unrelated to high blood pressure or NaCl intake.