Renal responses to hypoxemia during renin-angiotensin system inhibition in fetal lambs.
The role of the renin-angiotensin system (RAS) in modulating the renal hemodynamic and functional responses to hypoxemia was studied in chronically catheterized fetal lambs (132-143 days gestation; term 145 days) before and during administration of either captopril or [Sar1-Gly8]ANG II. Base-line mean arterial blood pressure decreased significantly after administration of either captopril or [Sar1-Gly8]ANG II. This decrease was associated with a significant decline in renal vascular resistance (RVR) in captopril-treated fetuses, whereas no changes in RVR were observed in [Sar1-Gly8]ANG II-treated fetuses. However, the decline in renal blood flow (RBF) and the rise in RVR associated with hypoxemia in control fetuses were not attenuated significantly during inhibition of the RAS using either captopril or [Sar1-Gly8]ANG II. Moreover neither captopril nor [Sar1-Gly8]ANG II blunted the hypertensive response associated with fetal hypoxemia. The renal functional response to captopril was different from the response observed during infusion of [Sar1-Gly8]ANG II. Administration of [Sar1-Gly8]ANG II produced significant decreases in urinary flow rate (UFR), glomerular filtration rate (GFR), and urinary electrolyte (Na+, K+, Cl-) excretion rates, whereas no changes were observed during captopril infusion. The effects of hypoxemia on renal function were not modified after captopril. However, [Sar1-Gly8]ANG II tended to increase UFR and GFR, but these changes were pressure-dependent and not directly related to inhibition of the RAS. This study suggests that the RAS is not an important mediator of the fetal renal hemodynamic and functional responses to hypoxemia.
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D002216:Captopril / Q000494:pharmacology; D005260:Female; D005315:Fetal Diseases / Q000503:physiopathology*; D005318:Fetal Heart / Q000503:physiopathology; D005919:Glomerular Filtration Rate; D006339:Heart Rate; D000860:Hypoxia / Q000503:physiopathology*; D007668:Kidney / Q000196:embryology / Q000503:physiopathology*; D011247:Pregnancy; D012079:Renal Circulation; D012084:Renin-Angiotensin System / Q000187:drug effects; D012756:Sheep / Q000502:physiology; D014655:Vascular Resistance
D000804:Angiotensin II; C010328:angiotensin II, Sar(1)-Gly(8)-; D002216:Captopril