Angiotensin II, renal nerves, and prostaglandins in renal hemodynamics during hemorrhage

The importance of renal prostaglandins (PG), angiotensin II, and renal nerves in control of renal hemodynamics was examined in anesthetized dogs during a 30% reduction in arterial blood pressure by hypotensive hemorrhage (HH). In the first group of eight PG-intact (control) animals, HH caused a modest decrease in both glomerular filtration rate (GFR) from 46 to 37 ml/min, p < 0.05) and renal blood flow (RBF) (from 254 to 192 ml/min, P < 0.01). In the second group of six dogs pretreated with indomethacin (10 mg/kg), a striking fall in both GFR (from 47 to 5 ml/min, P < 0.001) and RBF (from 213 to 25 ml/min, P < 0.001) was observed with HH. Unilateral intrarenal infusion of a specific angiotensin II antagonist (AIIA) in these depleted animals significantly attenuated this ischemic effect of HH as both GFR (5 vs. 20 ml/min, P < 0.005) and RBF (25 vs. 87 ml/min, P < 0.01) were higher in the AIIA-infused kidneys. To assess the combined influence of both renal nerves and the renin-angiotensin system as renal ischemic factors during HH, a third group of eight indomethacin-treated dogs underwent unilateral renal denervation and infusion of the AIIA antagonist prior to HH. The denervated, AIIA-infused kidneys in these PG-depleted animals had significantly greater GFR (41 vs. 5 ml/min, P < 0.005) and RBF (183 vs. 29 ml/min, P < 0.005) than the contralateral innervated, uninfused kidneys. Furthermore, this combination of renal denervation and AIIA infusion afforded significantly greater protection of GFR (41 vs. 20 ml/min, P < 0.05) and RBF (183 vs. 87 ml/min, P < 0.05) during HH than AIIA alone in the PG-depleted animals. The results, therefore, indicate that the renin-angiotensin system and renal nerves are major renal ischemic factors during HH of this degree, and these ischemic factors are normally opposed by renal PG.