It is well documented that acute insulin administration stimulates the sympathetic nervous system in both humans and animals. Despite marked sympathetic activation during acute hyperinsulinemia, blood pressure is generally not increased because it is overridden by the vasodilator action of insulin. The maintenance of blood pressure in the face of sympathetic activation is unknown. A possible mechanism includes feedback regulation by the baroreceptor reflex arc. In normotensive states, hyperinsulinemic-induced sympathetic activation may tend to elevate blood pressure, but this change is rapidly sensed by the baroreceptors in the carotid arteries (and aortic arch), and a counterbalancing increase in vasodilation could return blood pressure to normal. Thus, it can be speculated that, in the event of diminished baroreceptor sensitivity and suppressed vasodilator actions of insulin, common abnormalities in hypertension, acute insulin infusion would be expected to increase blood pressure. We undertook the present study to determine whether the baroreceptor reflex arc modulated the blood pressure response to acute hyperinsulinemia. To this end, six normotensive dogs underwent saline or insulin infusions before and after deactivation of the carotid and aortic baroreceptors. Baroreceptor dysfunction was documented after denervation in all cases by an abnormal response to phenylephrine injections. Before denervation, insulin infusions caused a slight but nonsignificant rise in mean arterial pressure (MAP; 110 +/- 5 to 120 +/- 5 mm Hg; P = 0.13). Baroreceptor denervation caused a marked variability in blood pressure. However, basal mean arterial pressure was not significantly altered. Neither saline nor insulin infusions (105 +/- 10 v 105 +/- 8 mm Hg, basal v steady state) caused a significant change in MAP in denervated dogs. Likewise, insulin and saline did not change heart rates significantly in intact or denervated animals. Furthermore, glucose metabolism was similar in both groups of animals. This study demonstrates that the baroreceptor reflex arc does not mediate the blood pressure response to acute hyperinsulinemia.