Although insulin is demonstrated to decrease vascular tone, the role of insulin in renal microcirculation has not been fully determined. In the present study, the effect of insulin on renal microvascular tone was assessed using the isolated perfused hydronephrotic rat kidney. Insulin (300 microU/ml) had no effect on the basal renal microvessel diameter. In addition, insulin did not alter myogenic (that is, pressure-induced) constriction of preglomerular microvessels, with similar magnitude of constriction of preglomerular microvessels, with similar magnitude of constriction observed in response to elevated renal perfusion pressure from 80 to 180 mm Hg (interlobular artery, -23 +/- 3% vs. -19 +/- 4%; afferent arteriole, -22 +/- 3% vs. -21 +/- 4%, for control and insulin, respectively). In striking contrast, insulin dose-dependently reversed the norepinephrine (NE)-induced tone of interlobular arteries, afferent arterioles, and efferent arterioles, with 94 +/- 9%, 104 +/- 6%, and 86 +/- 10% reversal at 300 microU/ml, respectively. These vasodilator actions were markedly inhibited by N-Arg; in the presence of N-Arg, insulin (300 microU/ml) exerted only a modest dilator action on interlobular arteries (24 +/- 9% reversal), afferent arterioles (23 +/- 10% reversal), and efferent arterioles (14 +/- 9% reversal). A similar renal microvascular responsiveness to insulin was also observed during angiotensin II (Ang II)-induced constriction. In conclusion, the ability of insulin to dilate the renal microvasculature differs, with marked inhibitory action during NE/Ang II-induced constriction and almost no inhibition during myogenic constriction. Furthermore, the present study suggests that the insulin-induced renal vasodilation is mediated by nitric oxide.