Acute renal hemodynamic effects of dimanganese decacarbonyl and cobalt protoporphyrin.
BACKGROUND
Heme oxygenase (HO) products have a protective role in acute renal failure (ARF) that may be hemodynamically mediated because the HO-derived carbon monoxide (CO) is an important control system of arteriolar tone. The vascular effects of HO may be caused directly through changes in CO synthesis, and indirectly by alterations in nitric oxide (NO) release. The present study evaluated in vivo the renal effects of a heme oxygenase inhibitor, Co(III)Protoporphyrin (CoPP) alone or in combination with the CO donor dimanganese decacarbonyl (Mn2(CO)10).


METHODS
All drugs were administered into the renal artery of anesthetized rats. Changes in renal cortical nitric oxide concentration were measured in vivo electrochemically.


RESULTS
The intrarenal administration of the CO donor Mn2(CO)10 increased blood carboxyhemoglobin levels (+74%), renal blood flow (+54%), glomerular filtration (+38%), and urinary cGMP excretion (+128%). On the other hand, the inhibition of renal HO with CoPP progressively induced an ARF characterized by a drop in renal blood flow (-77%), glomerular filtration (-93%), and urinary cGMP excretion (-93%). These deleterious effects of HO inhibition on renal function were nearly abolished by supplementing CO with the coadministration of Mn2(CO)10+ CoPP, indicating that they may be caused by inhibition of CO synthesis and the resulting hemodynamic changes. In addition, CoPP lowered the renal cortical NO concentration (-21%) and also decreased the urinary excretion of nitrates/nitrites, while Mn2(CO)10 increased renal NO levels (+20%) and raised the excretion of nitrates/nitrites, suggesting that changes in NO release may contribute to the renal effects of the HO-CO system.


CONCLUSIONS
These results indicate that heme oxygenase-derived CO plays a cardinal role in the control of renal hemodynamics and glomerular filtration.
Arregui
Begoña
B
Departamento de Fisiología, Facultad de Medicina, Murcia, Spain.
López
Bernardo
B
García Salom
Miguel
M
Valero
Fernando
F
Navarro
Concepción
C
Fenoy
Francisco J
FJ
D000818:Animals; D001663:Bilirubin / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002248:Carbon Monoxide / Q000378:metabolism; D006152:Cyclic GMP / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007672:Kidney Cortex / Q000098:blood supply / Q000378:metabolism; D008297:Male; D017895:Manganese Compounds / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014556:Urine
D004791:Enzyme Inhibitors; D017895:Manganese Compounds; D011524:Protoporphyrins; D009569:Nitric Oxide; C007095:cobaltiprotoporphyrin; D002248:Carbon Monoxide; C481647:dimanganese decacarbonyl; D006419:Heme Oxygenase (Decyclizing); D006152:Cyclic GMP; D001663:Bilirubin; D019331:NG-Nitroarginine Methyl Ester