Nitric oxide synthase inhibition exacerbates sepsis-induced renal hypoperfusion.

Abstract

Hyperdynamic sepsis is often complicated by renal dysfunction, caused in part by renal vasoconstriction and impaired blood flow. Nitric oxide (NO) is an important mediator of hemodynamic responses to sepsis; however, its importance in the renal microcirculation during sepsis is unknown. Our purpose was to determine the role of NO in the renal microcirculation during bacteremia. In vivo videomicroscopy was used to study the microcirculation in five groups of hydronephrotic rat kidneys. Cardiac output (CO), mean arterial pressure, interlobular artery (ILA) diameter and flow, and afferent (AFF) and efferent arteriole diameters were measured. NO synthase inhibition in normal rats resulted in hypertension, decreased CO, selective preglomerular constriction (ILA, -21%; AFF, -26% of baseline), and hypoperfusion (-56%). Escherichia coli resulted in a normotensive, high CO state (+23%) with ILA (-25%) and AFF (-20%) constriction and hypoperfusion (-60%). NO synthase inhibition during bacteremia normalized CO and increased mean arterial pressure (+34%) but exacerbated constriction (ILA, -45%; AFF, -33%) and further impaired flow (-90%). NO maintains preglomerular tone and flow during basal conditions and appears to counteract intrarenal vasoconstrictors during E. coli bacteremia.