EVIDENCE AGAINST A ROLE OF INSULIN IN HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS - CS-045 DOES NOT LOWER BLOOD-PRESSURE DESPITE IMPROVEMENT OF INSULIN-RESISTANCE

Hyperinsulinemia resulting from peripheral insulin resistance has been demonstrated both in spontaneously hypertensive rats (SHR) and in humans with essential hypertension. A new class of antidiabetic drugs, thiazolidinediones, which can improve insulin resistance, may be able to lower not only blood glucose levels but also blood pressure. The present study was therefore designed to clarify the proportion of SHR that are glucose intolerant and to observe the effect on blood pressure of CS-045 (troglitazone) administered at 70 mg/kg per day for 2 weeks to male SHR (n = 13). Among 67 male 8-week-old SHR, 74.6% were glucose intolerant and hyperinsulinemic. Systolic blood pressure did not correlate with plasma glucose or insulin levels before or after glucose loading. Treatment with CS-045 improved insulin resistance, as evidenced by a smaller area under the curve of plasma glucose and insulin levels in response to glucose loading. However, systolic blood pressure was not altered. When the data were reanalyzed according to the presence or absence of glucose intolerance before the treatment, blood pressure in the treated group was the same as in controls despite significant improvement in steady-state plasma glucose levels. These results suggest that hyperinsulinemia and/or insulin resistance may not be involved in the development or maintenance of hypertension in SHR, which is in contrast to models of hypertension such as obese Zucker rats or fructose-fed rats.