Abstract
tested whether rat descending vasa recta (DVR) undergo regulatory adaptations after the kidney is exposed to ischemia. Left kidneys (LK) were subjected to 30-min renal artery cross clamp. After 48 h, the postischemic LK and contralateral right kidney (RK) were harvested for study. When compared with DVR isolated from either sham-operated LK or the contralateral RK, postischemic LK DVR markedly increased their NO generation. The selective inducible NOS (iNOS) inhibitor 1400W blocked the NO response. Immunoblots from outer medullary homogenates showed a parallel 2.6-fold increase in iNOS expression ( P = 0.01). Microperfused postischemic LK DVR exposed to angiotensin II (ANG II, 10 nM), constricted less than those from the contralateral RK, and constricted more when exposed to 1400W (10 µM). Resting membrane potentials of pericytes from postischemic LK DVR pericytes were hyperpolarized relative to contralateral RK pericytes (62.0 ± 1.6 vs. 51.8 ± 2.2 mV, respectively, P < 0.05) or those from sham-operated LK (54.9 ± 2.1 mV, P < 0.05). Blockade of NO generation with 1400W did not repolarize postischemic pericytes (62.5 ± 1.4 vs. 61.1 ± 3.4 mV); however, control pericytes were hyperpolarized by exposure to NO donation from S-nitroso- N-acetyl- dl-penicillamine (51.5 ± 2.9 to 62.1 ± 1.4 mV, P < 0.05). We conclude that postischemic adaptations intrinsic to the DVR wall occur after ischemia. A rise in 1400W sensitive NO generation and iNOS expression occurs that is associated with diminished contractile responses to ANG II. Pericyte hyperpolarization occurs that is not explained by the rise in ambient NO generation within the DVR wall.