Susceptibility to Pressure‐induced Renal Injury in DOCA‐salt vs. Angiotensin II Hypertensive Rats

Abstract

Deoxycorticosterone acetate (DOCA) plus high salt diet feeding in rats is a low‐renin model of hypertension commonly used to investigate the pathogenesis of renal disease. Previous studies have reported that DOCA‐salt‐induced hypertension impairs renal blood flow (RBF) autoregulation; however, the susceptibility to blood pressure (BP)‐induced renal injury has not been determined. The goal of this study was to compare the BP‐renal injury and BP‐RBF relationships between DOCA‐salt and ANG II hypertensive rats.BP (radiotelemetry), proteinuria and renal injury were measured in male Sprague‐Dawley (SD) rats (Charles River) administered DOCA (3.3 mg/day s.c.) plus 1% NaCl + 0.2% KCl in the drinking water (n=15) and in rats administered ANG II (500 ng/kg/min s.c.) (n=12) for 6 weeks. The average 6‐week systolic BP was greater (P<0.05) in rats administered ANG II vs. DOCA‐salt (175±4 vs. 165±5 mmHg); however, proteinuria was not significantly different in ANG II vs. DOCA‐salt (60±11 vs. 86±15 mg/day) groups. A similar and modest level of glomerulosclerosis (GS) was seen in both ANG II (6±1%) and DOCA‐salt groups (7±3%); however, the slope of relationship between GS and BP was greater (P<0.05) in rats administered DOCA‐salt vs. ANG II (0.54 vs. 0.15 Δ%GS/ΔmmHg systolic BP). These data indicate that the susceptibility to BP‐induced renal injury is greater in DOCA‐salt vs. ANG II‐infused hypertensive rats.BP and RBF were measured in conscious chronically instrumented rats for 2–3 hours/day during 2–3 baseline recordings and over days 3–7 of DOCA‐salt (n=5) or ANG II (n=9) administration. We also assessed glomerular filtration rate (GFR) before and during DOCA‐salt administration. Robust and significant differences were observed in the average BP, RBF and renal vascular resistance (RVR) responses between groups. ANG II administration led to a 50% increase in mean BP (P<0.05), 100% increase in RVR (P<0.05) and 25% decrease in RBF (P<0.05). In contrast, while DOCA‐salt led to a more modest 11% increase in mean BP (P<0.05), RVR decreased by 25% (P<0.05) resulting in a 46% increase in RBF (P<0.05). The administration of DOCA‐salt did not significantly alter GFR. RBF autoregulation (changes in RBF during spontaneous changes in BP of 5 mmHg or greater) was assessed from the BP‐RBF recordings in conscious rats using recently developed novel methodologies. No effects of DOCA‐salt on RBF autoregulation were observed. In contrast, ANG II strengthened the RBF autoregulatory response, particularly within the first second following a change in BP of 5 mmHg or more.In summary, the reduced renal vascular tone in DOCA‐salt hypertensive rats may be contributing to its greater susceptibility to BP‐induced renal injury as compared to ANG II hypertensive rats. The augmentation of RBF autoregulatory responses by ANG II may also be contributing to the reduced susceptibility to BP‐induced renal injury in this model.Support or Funding InformationVeterans Administration, NIH