Inducible nitric oxide synthase inhibition attenuates renal hemodynamics during pregnancy

Abstract

Acute, nonselective nitric oxide synthase inhibition in the pregnant rat decreases glomerular filtration rate and renal plasma flow, suggesting a role for nitric oxide in mediating renal vasodilation during pregnancy. As mid-gestation in the rat is associated with a significant increase in renal protein expression of inducible nitric oxide synthase, the aim of this study was to examine the role of inducible nitric oxide synthase in mediating renal hemodynamics changes at mid-gestation in the rat. At day 16 of pregnancy, glomerular filtration rate was significantly higher in pregnant rats compared with virgin rats (3.1±0.4 versus 2.7±0.3 mL/min, respectively; P<0.05), as was effective renal plasma flow (13.4±2.5 versus 10.9±2.2 mL/min, respectively; P<0.05). Acute administration of the inducible nitric oxide synthase selective inhibitor, AMT hydrochloride (750 nmol/h), markedly attenuated the increase in glomerular filtration rate observed in pregnant rats (2.3±0.2 mL/min, P<0.01 versus pregnant) without significantly altering glomerular filtration rate in virgin rats (2.1±0.2 mL/min). Acute AMT administration significantly decreased effective renal plasma flow in pregnant (8.9± 1.8 mL/min, P<0.01 versus pregnant) and virgin rats (7.1±0.9 mL/min, P<0.05 versus virgin). Acute administration of EIT (380 nmol/h), another inducible nitric oxide synthase selective inhibitor, also attenuated pregnancy-induced increases in glomerular filtration rate (2.1 ±0.2, 2.8±0.3, and 2.3±0.3 mL/min; virgin, pregnant, and EIT, respectively) and effective renal plasma flow (8.5±1.1, 13.8±2.1, and 9.0±1.1 mL/min; virgin, pregnant, and EIT, respectively). Therefore, these findings suggest that inducible nitric oxide synthase may play an important role in mediating the renal hemodynamic changes that occur during normal pregnancy.