Loss of the glomerular contractile response to angiotensin in rats following myohemoglobinuric acute renal failure.
To examine the state of the glomerulus in rats protected from acute renal failure (ARF) by prior insult, we measured the contractile responses of isolated glomeruli to angiotensin II (AII) and dibutyryl cyclic AMP (DBcAMP). In healthy rats, both agents induced a dose-related fall in glomerular diameter (P less than 0.001). Saralasin, the angiotensin antagonist, blocked the glomerular response to AII totally and to DBcAMP partially. Two weeks following ARF induced with 50% glycerol (10 ml/kg, im), azotemia had reversed and the nephrotoxic effect of mercuric chloride (4.7 mg/kg, sc) was blunted, as anticipated. AII did not reduce glomerular size, but the response to DBcAMP was sustained at this time. To determine the specificity of the loss of the glomerular response to AII, we also assessed the effects of an AII infusion (1 microgram/kg/min) on blood pressure and renal blood flow. There was a substantial rise in blood pressure (control, 104 +/- 11.8 mm Hg; AI, 131.0 +/- 5.3 mm HG; P less than 0.001) and fall in renal blood flow (control, 2.45 ml/g per min; AII, 0.81 +/- 0.10 ml/g per min; P less than 0.025). Vascular responsiveness to AII was preserved at a time when glomeruli were totally unresponsive and rats were resistant to ARF. The loss of glomerular contractility may, in part, account for the protection from ARF seen in this model: if so, glomerular abnormalities may play a pathogenetic role.
D058186:Acute Kidney Injury / Q000150:complications*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005990:Glycerol / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009212:Myoglobinuria / Q000150:complications*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D000804:Angiotensin II; D003994:Bucladesine; D005990:Glycerol