Introduction
The role of nitric oxide in the hemodynamic autoregulation of the kidney is controversial. It has been found to dilate the renal vasculature, and blockade of NO synthesis has been reported to improve the efficiency and extend the lower limit of autoregulation, at least in certain models. We analyzed the vascular effects of the endothelial NO system in afferent arterioles in the juxtamedullary nephron preparation.
Methods
5-5 Sprague-Dawley male rats (240-300 g) were used in Series 1 and Series 2 self-controlled experiments. The left kidney was prepared as described originally by Casellas (1) and perfused with Krebs-Ringer-bicarbonate solution containing 4% albumin (gassed with a 95% O2/5% CO2 mixture) during control conditions which was then supplemented with either L-NAME (10-4 M, Series 1) or red blood cells (20% Ht, Series 2). The renal perfusion pressure was first set to 50 mmHg, then stepwise elevated to 75, 100, 125 and 150 mmHg, then it was brought back to 50 mmHg again. Following addition of red cells or L-NAME the same pressure manipulations were repeated. The diameters of the afferent arterioles (AA) were recorded videometrically at every step.
Results
Series 1: AA diameters (Mean±SD) recorded during the control period were 22.7±2.0; 25.6±2.4 (+12.6±10.5%); 27.3±2.5 (+20.1±11.1%); 28.4±2.2 (+25.3±9.6%); 29.4±2.3 mm (+29.7±10.3%) at 50, 75, 100, 125, and 150 mmHg pressure, respectively. Following addition of L-NAME, the diameters were 20.1±1.4; 18.5±1.7 (-8.1±8.5%); 17.6±1.5 (-12.4±7.5%); 17.1±1.6 (-14.9±7.9%); 16.5±1.3 mm (-17.9±6.5%). In Series 2, AA diameters during the control period were 21.3±1.1; 23.6±2.1 (+10.8±9.8%); 24.7±1.9 (+16.1±8.9%); 26.3±2.4 (+23.5±11.2%); 27.3±3.7 mm (+28.4±17.5%). Following addition of red blood cells, the diameters became 18.6±1.0; 17.6±1.8 (-5.4±9.6%); 15.7±1.0 (-15.6±5.3%); 15.2±1.9 (-18.4±10.3%); and 14.0±1.3 mm (-24.7±6.9%). The calculated AA flows were 1.36 and 12.72 vs. 0.28 and 0.25 ml/min at 50 and 150 mmHg respectively (control vs. L-NAME, Series 1) and 0.86 and 9.84 vs. 0.17 and 0.23 ml/min (control vs. RBC, Series 2).
Conclusions
AA perfused with cell-free perfusate lose their ability to autoregulate. Because of the lack of hemoglobin, an effective scavenger of the endothelial NO, excessive amounts of NO reach the vascular smooth muscle cells causing dilation and loss of autoregulation. Addition of RBC’s to the perfusate or blockade of the NO production "restore" autoregulation. The effective NO concentration seems to be a result of endothelial production and intraluminal scavenging.
References
(1) Casellas, D., Navar, L.G.: In vitro perfusion of juxtamedullary nephrons in rats. Am J Physiol 246 (Renal Fluid Electrolyte Physiol 15): F349-F358, 1984.