Differences in vascular reactivity in models of ischemic acute renal failure.
To determine the mechanism of observed differences in vasoreactivity in norepinephrine-induced (NE) and renal artery clamp (RAC) models of ischemic acute renal failure (ARF), induction renal blood flow (RBF) was measured and vascular reactivity examined one week thereafter in NE- and RAC-ARF rat kidneys that had identical levels of renal dysfunction. Morphology also was compared at 48 hours and one week. In NE-ARF, RBF was 14% during 90 minutes of induction and by 60 minutes post-NE infusion was only 18% of baseline. In contrast, in RAC-ARF RBF was effectively 0 for 75 minutes but returned to 95% of baseline by 60 minutes after clamp release. At one week there was a paradoxical increase in renovascular resistance (RVR) to renal perfusion pressure (RPP) reduction in the autoregulatory range and an augmented vasoconstriction to renal nerve stimulation (RNS) in NE-ARF, but no change in RVR and minimal reduction in RBF to these same respective stimuli in RAC-ARF (both different at P less than 0.001). NE-ARF were more sensitive to intrarenal norepinephrine than RAC-ARF kidneys (P less than 0.001). Neither NE- nor RAC-ARF kidneys responded to endothelium-dependent acetylcholine (ACh). Vasodilation to endothelium-independent prostacyclin (PGI2) in NE- was similar to sham-ARF, but there was an attenuated response in RAC-ARF kidneys (P less than 0.001). Morphology at 48 hours showed smooth muscle necrosis in half of the resistance vessels in RAC- but in less than 10% of those in NE-ARF. Except for a slightly greater frequency of tubular casts at 48 hours in RAC-ARF, tubular injury was indistinguishable. It is concluded that NE-ARF has evidence of a predominant functional endothelial vascular injury while RAC-ARF has both morphologic and functional evidence of a predominant smooth muscle injury. Differences in vascular injury between the two models, at least in part, may be the consequence of differences in severity of initial ischemia and/or the rates of recovery of RBF; however, an additional or separate toxic effect of infused NE cannot be excluded.
Conger
J D
JD
University of Colorado Health Sciences Center, Denver.
Robinette
J B
JB
Hammond
W S
WS
D000109:Acetylcholine / Q000494:pharmacology; D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001808:Blood Vessels / Q000503:physiopathology; D004558:Electric Stimulation; D011464:Epoprostenol / Q000494:pharmacology; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000294:innervation / Q000473:pathology; D009420:Nervous System / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects
D011464:Epoprostenol; D000109:Acetylcholine; D009638:Norepinephrine