Changes in renal microcirculation induced by infusion of (Fe3+)-and (Fe2+)-myoglobin during hemorrhagic hypotension in the anesthetized rat: influence of L-NAME and 8-Br-cyclic GMP.
The effects of myoglobin on renal microcirculation were studied in anesthetized rats subjected to hemorrhagic hypotension. Capillary flow distribution was determined by allowing two dyes to circulate for 3 and 1 min, respectively, freezing the left kidney and quantifying the dye distribution in histological sections by analyzing the distances of regularly spaced test points to the next dye-labeled capillary. Control experiments showed 88% of distances to be < 12 microns in the cortex [medullary outer stripe (OS): 77%, inner stripe (IS): 93%] and no distance to be > 60 microns. Myoglobin induced disturbances in intrarenal perfusion with a significantly higher potency of (Fe2+)- as compared to (Fe3+)-myoglobin. With the reduced species, the fraction of distances > 60 microns increased to 54% in the cortex (OS: 69%; IS: 67%). L-NAME, an inhibitor of nitric oxide synthesis, induced similar defects of perfusion. The cGMP analogue 8-Br-cGMP was able to nearly completely prevent these effects. The results support the view that myoglobin when released during hemorrhagic hypotension impairs renal microcirculation supposedly by scavenging the endogenous relaxing factor nitric oxide.
Vetterlein
F
F
Department of Pharmacology and Toxicology, University of Göttingen, Germany.
Reimers
A
A
Schmidt
G
G
D000771:Anesthesia, Intravenous; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006470:Hemorrhage / Q000473:pathology / Q000503:physiopathology*; D007022:Hypotension / Q000473:pathology / Q000503:physiopathology*; D007501:Iron / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009211:Myoglobin / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D009211:Myoglobin; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D007501:Iron; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester