Disparate effects of insulin on isolated rabbit afferent and efferent arterioles

Abstract

Despite evidence that insulin per se may be an important regulator of glomerular hemodynamics, little is known about its direct action on the glomerular afferent arterioles (Af-Art) and efferent arterioles (Ef-Art), the crucial vascular segments that control glomerular hemodynamics. In the present study, we examined the direct effect of physiological concentrations of insulin on isolated microperfused rabbit Af- and Ef-Arts. After cannulation, vessels were equilibrated in insulin-free medium for 30 min. To determine whether insulin causes vasodilation or constriction, increasing doses (5, 20, and 200 microU/ml) were added to the bath and lumen of arterioles that were either preconstricted to 50% of control diameter with norepinephrine or left nonpreconstricted. Insulin caused no vasoconstriction in either Af- or Ef-Arts, but it reversed norepinephrine-induced constriction in Ef-Arts but not Af-Arts (suggesting a vasodilator action selective to the Ef-Art): at 200 microU/ml, insulin increased Ef-Art luminal diameter by 75.8 +/- 7.0% from the preconstricted level (n = 6; P < 0.008). The vasorelaxant effect of insulin on Ef-Arts was not affected by blockade of either endothelium-derived relaxing factor/nitric oxide or prostaglandin synthesis. Despite the lack of effect of insulin on Af-Art when added after the equilibration period, when Af-Arts were equilibrated in the presence of either 20 or 200 microU/ml insulin, their basal diameter was significantly reduced (11.7 +/- 0.9 microns; P < 0.025, n = 6, and 12.0 +/- 0.9 microns; P < 0.025, n = 7, respectively) compared with nontreated Af-Arts (16.2 +/- 1.3 microns; n = 7). In conclusion, this study demonstrates that at physiological concentrations, insulin dilates NE-constricted Ef-Arts, while insulin pretreatment enhances Af-Art tone. The disparate actions of insulin on the Af- vs the Ef-Art may contribute to its beneficial effect on glomerular hypertension.