Effects of exogenous heme on renal function: role of heme oxygenase and cyclooxygenase.
We examined the effects of heme administration (15 mg/kg IV) on indexes of renal carbon monoxide production and contrasted the renal functional response to heme in anesthetized rats pretreated and not pretreated with stannous mesoporphyrin (40 micromol/kg IV) to inhibit heme oxygenase or sodium meclofenamate (5 mg/kg IV plus infusion at 10 microg/kg per minute) to inhibit cyclooxygenase. In rats without drug pretreatment, heme administration decreased renal vascular resistance and increased renal blood flow, urine volume, and sodium excretion associated with augmented urinary excretion of 6-keto-PGF1alpha and enhanced concentration of carbon monoxide in the renal cortical microdialysate. Pretreatment with stannous mesoporphyrin did not prevent heme from producing renal vasodilation and increasing renal blood flow but abolished the diuretic and natriuretic responses. Conversely, pretreatment with sodium meclofenamate blunted the renal vasodilatory effect of heme but affected neither the diuretic nor the natriuretic effect. We conclude that heme-induced renal vasodilation is a cyclooxygenase-dependent response involving increased synthesis of PGI2, whereas heme-induced diuresis and natriuresis are heme oxygenase-dependent responses involving inhibition of tubular reabsorption of sodium and water through undefined mechanisms.
Rodriguez
Francisca
F
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA. francisca_rodrigues@nymc.edu
Kemp
Rowena
R
Balazy
Michael
M
Nasjletti
Alberto
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002248:Carbon Monoxide / Q000652:urine; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006418:Heme / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D008665:Metalloporphyrins / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011460:Prostaglandins F / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011460:Prostaglandins F; C055421:tin mesoporphyrin; D006418:Heme; D008469:Meclofenamic Acid; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D011451:Prostaglandin-Endoperoxide Synthases; C100006:prostaglandin F1