Tubuloglomerular feedback, prostaglandins, and angiotensin in the autoregulation of glomerular filtration rate.
To define the mechanisms responsible for autoregulation of SNGFR in the subnormal pressure range, the response of SNGFR to graded reductions of arterial pressure was measured before and after interfering with the tubuloglomerular feedback system (TGF), angiotensin II action and prostaglandin (PG) synthesis. Studies were performed in male Sprague-Dawley rats in which estimated surgical plasma losses were replaced, because euvolemic animals were found to have better autoregulatory capacity than hydropenic animals. In control plasma-replaced animals, a pressure reduction from normal to 97.5 mm Hg and a further reduction to 78 mm Hg had no significant effect on SNGFR (31.8 +/- 1.32 to 31.7 +/- 1.6 to 29.3 +/- 1.48 nl/min) when all autoregulatory mechanisms were intact. After eliminating TGF, the same pressure steps were followed by significant reductions in SNGFR (40.8 +/- 1.75 to 36.4 +/- 2.18 to 31.0 +/- 1.56 nl/min). During infusion of saralasin (1 microgram/kg X min), SNGFR did not change significantly during reduction of pressure from normal to 95.5 mm Hg (32.0 +/- 1.02 to 30.7 +/- 1.58 nl/min) but fell when pressure was reduced to 77 mm Hg (26.0 +/- 1.19 nl/min). Infusion of this dose of saralasin was without significant effect on the response of early proximal flow rate to loop of Henle perfusion. During indomethacin-induced inhibition of PG synthesis, SNGFR fell significantly in response to both pressure steps (38.6 +/- 1.4 to 34.0 +/- 1.68 to 25.5 +/- 1.29 nl/min). An analysis of the autoregulatory components indicates that in the higher pressure interval 115 to 95 mm Hg, TGF contributes about 50% and PG's about 30% to autoregulatory adjustments. In the lower pressure interval, 95 to 78 mm Hg, 30% autoregulatory compensation occurs through the TGF mechanism and 20% depends upon the action of angiotensin II. Probably in part by interfering with both of those mechanisms, inhibition of PG synthesis reduces autoregulatory compensation by about 60%.
D000818:Animals; D001794:Blood Pressure; D001834:Body Water / Q000502:physiology; D015232:Dinoprostone; D005246:Feedback; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006706:Homeostasis; D007213:Indomethacin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000502:physiology*; D007684:Kidney Tubules / Q000502:physiology*; D008297:Male; D009399:Nephrons / Q000502:physiology; D011458:Prostaglandins E / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System; D012504:Saralasin / Q000494:pharmacology
D011458:Prostaglandins E; D012504:Saralasin; D015232:Dinoprostone; D007213:Indomethacin