Renal function of substance P in rats chronically exposed to hypoxia

Background: We studied the renal action of substance P (SP) in rats chronically exposed to hypoxia (high altitude, HA), compared to control rats kept at sea level (SL). Methods: Hypoxia was induced by placing female Wistar rats (182-225 g) in an altitude chamber (5500 m) 15 h · d^-1 for 4 weeks. Results: Intrarenal arterial infusion of substance P (60 ng · kg^-1 · h^{- 1}) increased the excretion of urine, sodium in both groups of rats, however, the excretion of kallikrein (KK) and the glomerular filtration rate (GFR) were not significantly altered. After aprotinin (10,000 kiu · kg^-1 · min^-1) treatment, kallikrein was depleted and substance P lost its diuretic action. Spantide, an SP antagonist (6000 ng · kg^-1 · h^-1, I.V.) decreased urine, and urinary excretion of sodium and potassium in SL rats, but not in HA rats. Acute renal denervated diuresis in SL rats was not modified after Spantide administration. Finally, it was found that both SP and SP antagonist did not significantly change the renal parameters in either group of rats after chronic renal denervation. Conclusion: We made the following conclusions: a) endogenous renal action of SP was suggested in SL but not in HA rats; b) the renal action of SP might be through KK release, although urinary KK did not increase after SP administration; and c) SP action is renal nerve dependent in both groups of rats.