The Role of the NADPH Oxidase Subunit p67phox in the Regulation of Renal Blood Flow in Dahl S (SS) Rats
Authors: Evans Louise C , Polichnowski Aaron J , Cowley Allen W 
Published: November 2023

Autoregulation of renal blood flow (RBF) is a defense mechanism by which the kidney protects itself from hypertensive injury. In the face of increased mean arterial pressure (MAP), mechanisms within the kidney ensure that both RBF and glomerular filtration rate (GFR) remain stable. We have reported that GFR is significantly reduced in SS rats following 14‐days of a 4.0% NaCl high salt (HS) diet. SS rats in which p67phox, a cytosolic component of NADPH‐oxidase, has been genetically mutated (SSp67phox−/−) have an attenuated hypertensive response, reduced renal injury and maintained GFR when fed a HS diet. We hypothesize that the increased renal injury and reduced GFR in the SS rat is the result of impaired renal autoregulation in the face of salt‐sensitive hypertension. Studies examining renal autoregulation have been predominantly performed in anesthetized rats. These studies are confounded by the effect of anesthesia and the acute responses to changes in MAP may not reflect the chronic responses which occur in conscious animals. In the current study we sought to analyze, chronologically, changes in RBF in response to increased MAP in conscious SS and SSp67phox−/− rats during chronic salt loading.

Male SS and SSp67phox−/− rats surgically prepared at 10–12 weeks (n=3–6) were maintained from birth on a 0.4% NaCl diet and prior to surgery trained to a bidirectional turnable cage. To assess changes in RBF transonic flow probes were placed around the left renal artery. MAP was measured from indwelling carotid catheters by telemetry. Following 7 days of recovery, RBF and MAP were recorded 24hr/day. Baseline measurements were made over 3 days to obtain stable control measurements on 0.4% NaCl, after which the salt content of the diet was increased to 4.0% and measurements continued for 14‐days.

During the control period, RBF was substantially higher in SS rats than the SSp67phox−/− rats (7.9±0.5ml/min and 5.15±0.2ml/min respectively). Both MAP and RBF displayed a circadian rhythm, with the highest values being recorded during the active period and the lowest during the inactive period. RBF increased progressively in the SSp67phox−/− rats in response to a HS diet. RBF was significantly higher than control values from HS7 and at HS14 averaged 7.9±0.6ml/min. MAP increased progressively in the SSp67phox−/− rats (from 114±5 to 128±6 mmHg) and consequently renal vascular resistance did not change throughout the study. RBF remained higher in the SS rats than SSp67phox−/− rats throughout the salt challenge, averaging 9.13±1.7ml/min at HS14. The pressor response to HS was augmented in the SS rats, increasing from 119±5 to 144±5 mmHg.

These studies have used the chronic assessment of RBF to track the renal response to increased MAP. The data suggest that chronic increases in MAP result in augmented RBF. This is in contrast to the results obtained in anesthetized rats, highlighting the importance of making physiological measurements in conscious animals. We propose that sustained increases in MAP result in augmented RBF in SS which rats may contribute to their increased propensity for renal injury during chronic salt challenges.