CONTRIBUTION OF THE SYMPATHETIC NERVOUS-SYSTEM TO HYPERTENSIVE RESPONSE TO INSULIN EXCESS IN SPONTANEOUSLY HYPERTENSIVE RATS

Our previous studies demonstrate that chronic insulin administration e xacerbates hypertension in spontaneously hypertensive rats (SHR). In t he present study, we tested the hypothesis that the presser effect of insulin in SHR is medicated by sympathetic nervous system overactivity . Male SHR (7 weeks old) were given daily subcutaneous injection of in sulin or vehicle for 3 days, after which each rat received an intraven ous infusion of the peripheral ganglionic blocker hexamethonium. Two d ays later, in a second experiment, the infusion protocol was repeated with the alpha(2)-adrenoceptor agonist clonidine, which more selective ly inhibits sympathetic (as compared with parasympathetic) nervous sys tem activity. Insulin treatment for 3 days caused a significant increa se in mean arterial pressure (MAP; 164 +/- 2 mm Hg vs. saline control 148 +/- 3 mm Hg), but ganglionic blockade with hexamethonium eliminate d the difference in blood pressure (BP) between the insulin-treated an d control SHR. Infusion of clonidine significantly reduced MAP in the insulin-treated group to the level of the untreated control SHR, but t he infusion did not reduce MAP in the latter group. In a second group of rats, acute administration of prazosin also eliminated the differen ce in MAP between insulin-treated and control SHR. We conclude that in SHR the sympathetic nervous system contributes importantly to the pre sser effect of insulin administration and that this effect may be medi ated by the central nervous system.