Submitted on July 9, 2007
Accepted on January 22, 2008
Hyperinsulinemic rats are normotensive but sensitized to angiotensin II
Maria E Johansson1, Irene J Andersson2, Camilla Alexanderson3, Ole Skott4, Agneta Holmang3, and Goran Bergstrom5*
1 Department of Molecular and Clinical Medicine/Clinical Physiology, Inst of Medicine, Sweden
2 Dept of Physiology, Institute of Neuroscience and Physiology, Sweden
3 Dept of Physiology, Institute of Neuroscience and Physiology,, Goteborg, Sweden
4 Physiology and Pharmacology, U Southern Denmark, Odense, Denmark
5 Department of Molecular and Clinical Medicine/Clinical Physiology, Inst of Medicine, Goteborg, Sweden
* To whom correspondence should be addressed. E-mail: goran.bergstrom{at}hjl.gu.se.
The effect of insulin on blood pressure is debated and an involvement of an activated renin-angiotensin aldosterone system (RAAS) has been suggested. We studied the effect of chronic insulin infusion on telemetry BP and assessed sympathetic activity and dependence of the RAAS. Female Sprague Dawley rats received insulin (2 IU/day, INS, n=12) or insulin combined with losartan (30 mg/kg/day, INS-LOS, n=10), the angiotensin II receptor antagonist, for six weeks. Losartan-treated (LOS, n=10) and untreated rats served as controls (C, n=11). We used telemetry to measure BP and heart rate (HR), and acute ganglion blockade and air-jet stress to investigate possible control of BP by the sympathetic nervous system. In addition, we used myograph technique to study vascular function ex vivo. INS and INS-LOS developed euglycemic hyperinsulinemia. Insulin did not affect BP but increased HR (27 beats/min on average). Ganglion blockade reduced mean arterial blood pressure (MAP) similarly in all groups. Air-jet stress did not increase sympathetic reactivity but rather revealed possible blunting of the stress response in hyperinsulinemia. Chronic losartan markedly reduced 24-hour-MAP in the INS-LOS group (-38 ± 1 mmHg P<0.001) compared with the LOS group (-18 ± 1mmHg, P
0.05). While insulin did not affect vascular function per se, losartan improved endothelial function in the aorta of insulin treated rats. Our results raise doubt regarding the role of hyperinsulinemia in hypertension. Moreover, we found no evidence that insulin affects sympathetic nervous system activity. However, chronic losartan treatment revealed an important interaction between insulin and RAAS in blood pressure control.
