Insulin Infusion in Conscious Dogs

Abstract

A B S T R A C T Cardiovascular actions of insulin were studied by intravenous infusions of insulin (4 and 8 mU/kg per min) in normal conscious dogs. This resulted in increases in cardiac output, heart rate, and left ventricular derivative of pressure with respect to time (dP/dt) and dP/dt/P, as blood glucose was reduced. The inotropic and chronotropic effects of insulin were not related to hypoglycemia, as they persisted even when blood glucose was restored to control values or when it was prevented from falling by a simultaneous infusion of glucose. These cardiac effects were accompanied by increases in plasma catecholamines, and were abolished by propranolol pretreatment. Both plasma epinephrine and norepinephrine increased during insulin hypoglycemia, but only norepinephrine increased during insulin infusion when euglycemia was maintained.Mean arterial blood pressure did not change significantly during insulin hypoglycemia, but rose if euglycemia was maintained, probably due to the selective increase in norepinephrine in the latter condition. A pressor response also occurred in propranolol-pretreated dogs during insulin hypoglycemia, but was abolished when the animals also had been pretreated Insulin infusion increased left ventricular work and myocardial blood flow in dogs with and without hypoglycemia. Myocardial blood flow, however, did not change significantly during insulin infusion in dogs pretreated with propranolol. As propranolol also diminished the inotropic response, it appears that the increase in myocardial blood flow caused by insulin in the normal dog is causally related to the increased myocardial metabolic demand.Insulin also produced vasomotor effects on other vascular beds. In skeletal muscle, blood flow was increased under all study conditions, except during insulin hypoglycemia after propranolol-pretreatment when unopposed alpha-mediated vasoconstriction was present. The persistent increase in flow during both alpha and beta adrenergic blockade suggests that insulin has a direct dilator effect on skeletal muscle vasculature. In the adrenal gland, flow was increased except during euglycemia, when no rise in plasma epinephrine was observed, suggesting coupling between adrenal flow and catecholamine release. In the splanchnic bed, flow was decreased during euglycemia, when plasma norepinephrine rose, and during beta adrenergic blockade with propranolol, when unopposed alpha-mediated vasoconstriction also predominated. A similar pattern was found in the kidney, except that renal blood flow also fell after combined alpha and beta adrenergic blockade. The results show that the vasomotor effects on regional flows are mediated both via adrenergic mechanisms, and in the case of skeletal muscle and kidney, via mechanisms unrelated to sympathetic stimulation.

Circulatory and Metabolic Effects of Hypoxia in the Hyperinsulinemic Ovine Fetus

“…The importance of sympathoadrenal stimulation in support of hemodynamic homeostasis in the hyperinsulinemic adult and fetus has been well documented (9,11,12,15,22,26). In an earlier study (ll), we showed that hyperinsulinemic hypoglycemia results in increases in both peripheral plasma norepinephrine and epinephrine concentrations.…”

“…Under baseline oxygen availability in the hyperinsulinernic state compromises conditions, oxygen extraction of the heart is near maximal. some aspects of the fetal compensatory response to hyperinConsequently, during hyperinsulinemia in adult dogs (26), the sulinemia, there are no major qualitative differences in the increase in myocardial oxygen consumption is achieved by responses of hyperinsulinernic and normal fetuses to hypoxia. increases in perfusion rather than oxygen extraction.…”

Insulin attenuates agonist-mediated calcium mobilization in cultured rat vascular smooth muscle cells.

“…While chronic hyperinsulinemia is thought to contribute to hypertension through several mechanisms including abnormal renal sodium han-dling (4,7,8), increased sympathetic nerve activity (8)(9)(10), and vascular reactivity (7), the acute action of insulin is vasodilatory as shown both in vivo ( 1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14], and in isolated vascular tissue ( 15,16).…”

Modulation of β‐oxidation and proton conductance pathway of brown adipose tissue in hypo‐ and hyperinsulinemic states

“…These results raise the question whether the observed effects of hyperinsulinemia are due to a direct action of insulin on BAT metabolic activity or are secondary to the increased sympathetic activity induced by either insulin or hypoglycemia. It was reported that insulin exerts a direct stimulatory action on the sympathetic nervous system independent of hypoglycemia in the rat [7], in the dog [24] and in man [25]. In insulininfused rats, the plasma levels of catecholamines were slightly increased [12] but this was probably insufficient in itself to account for the observed effects on IBAT since the highest levels measured in the plasma are still about two orders of magnitude lower than those required to stimulate IBAT metabolism [3].…”