Nitric oxide release in the renal circulation of normoxia-or hypoxia-adapted rats in response to acute local hypoxia

Abstract

Nitric oxide (NO) and the kidneys may play a role in hypoxia induced hypertension. However, it is uncertain whether acute hypoxia, or the adaptation to chronic hypoxia, affects NO release from renal blood vessels. In anesthetized normoxic Sprague-Dawley rats (Nx), a kidney was vascularly isolated and perfused with 80% O2 buffer. Renal venous effluent was used to determine NO metabolites via the Griess reaction. Acute local hypoxia (15 mins) was induced by use of a 15% O2 buffer. This was repeated in rats kept in a 10% O2 chamber for 2 weeks prior to the experiment (Hx). Renal venous NO metabolites (RVNO) in Nx rats increased from 4.08 ( 0.03 to 4.29 ( 0.08 (M (P<0.02) in the first 5 minutes of local hypoxia, but returned to control levels subsequently. RVNO in Hx, during control period, were not significantly different from those in Nx. However, they failed to increase in Hx during the first 5 mins of acute hypoxia, and were lower (P < 0.02) than those in Nx. They also decreased from 4.07 ( 0.04 to 3.97 ( 0.04(M (P < 0.05) in Hx during the final 5 mins of acute hypoxia. Acetylcholine (0.2mL x 2(M), as a positive control, increased RVNO in both Nx (4.08 ( 0.03 to 4.22 ( 0.02 (M; P<0.003) and Hx (3.92 ( 0.07 to 4.15 ( 0.07(M; P<0.007).Local hypoxia failed to stimulate RVNO from Hx. Response to acetylcholine rules out endothelial damage. This inability to respond to hypoxic stress may help explain the development of systemic hypertension in Hx rats.