Renal and tubuloglomerular feedback effects of [Sar1,Ala8]angiotensin II in the rat.
Experiments were done in normal rats to assess kidney, single nephron, and tubuloglomerular feedback responses during control conditions and during renin-angiotensin blockade with the angiotensin II (ANG II) antagonist [Sar1,Ala8]angiotensin II (saralasin, 20 micrograms.kg-1.min-1). Plasma renin activity was increased fourfold during saralasin infusion. Glomerular filtration rate (GFR) and renal blood flow increased in parallel from 1.09 +/- 0.04 to 1.26 +/- 0.05 ml/min and from 6.4 +/- 0.5 to 7.6 +/- 0.5 ml/min, respectively. Absolute and fractional sodium excretion were increased sixfold during ANG II blockade. Hydrostatic pressures in proximal tubules, peritubular capillaries, and distal tubules were unchanged. Estimates of nephron GFR (SNGFR) based on collections of distal tubular fluid were increased from 21.6 +/- 1.2 to 24.3 +/- 0.9 nl/min during ANG II blockade. Increases in SNGFR and decreases in fractional absorption at micropuncture sites beyond the late proximal tubule during saralasin administration resulted in increases of flow rate and Cl- delivery at the early distal tubule. Tubuloglomerular feedback activity, assessed by measuring changes in proximal tubule stop-flow pressure in response to alterations in orthograde microperfusion rate from late proximal tubule sites, was significantly attenuated over the range of physiological flow rates for the late proximal tubule during blockade of the renin-angiotensin system. Acute blockade of ANG II in this rat model results in attenuated tubuloglomerular feedback activity and associated changes of hemodynamic and excretory behavior by the kidney.
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000097:blood; D000818:Animals; D005246:Feedback; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000502:physiology*; D007678:Kidney Glomerulus / Q000502:physiology*; D007684:Kidney Tubules / Q000502:physiology*; D009399:Nephrons / Q000502:physiology*; D009997:Osmotic Pressure; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000494:pharmacology*
D000804:Angiotensin II; D012083:Renin; D012504:Saralasin