Nitric oxide synthase inhibition aggravates intestinal microvascular vasoconstriction and hypoperfusion of bacteremia.

Abstract

Nitric oxide (NO) is an important hemodynamic mediator of sepsis; however, its visceral microcirculatory effects are largely unknown. To determine the role of systemic nitric oxide synthase (NO-S) inhibition on the microcirculation of the small intestine (SI), an intact loop of SI was exteriorized from decerebrate rats into a controlled tissue bath. Videomicroscopy was used to measure arteriolar diameters (A1, A3) and optical Doppler velocimetry was used to quantitate flow. In nonbacteremic controls inhibition of NO-S by N omega-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg IV) caused vasoconstriction (A1 = -7%; A3 = -24% baseline values) and reduced A1 flow by 26%. Bacteremic controls received 10(9) Escherichia coli IV, which resulted in arteriolar constriction and hypoperfusion (A1 = -16%; A3 = -21%; A1 flow = -44%), despite increased cardiac output (+33%). Treatment of bacteremic rats with L-NAME corrected the increased cardiac output (-3%), but exacerbated vasoconstriction (A1 = -24%; A3 = -27%) and did not improve A1 flow (-49%). These data indicate that (1) NO mediates basal microvascular tone of the SI; (2) hyperdynamic bacteremia causes arteriolar constriction and hypoperfusion of the SI; and (3) although systemic NO-S inhibition normalizes cardiac output and increases blood pressure, it aggravates vasoconstriction in the SI and does not improve hypoperfusion.