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(Hypertension. 2003;42:680.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Effects of Exogenous Heme on Renal Function

Role of Heme Oxygenase and Cyclooxygenase

Francisca Rodriguez; Rowena Kemp; Michael Balazy; Alberto Nasjletti

From the Department of Pharmacology, New York Medical College, Valhalla, NY.

Correspondence to Francisca Rodriguez, PhD, Department of Pharmacology, New York Medical College, Valhalla, NY 10595. E-mail francisca_rodrigues{at}nymc.edu

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 µmol/kg IV) to inhibit heme oxygenase or sodium meclofenamate (5 mg/kg IV plus infusion at 10 µg/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-PGF₁ 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.

Key Words: kidney • renal circulation • prostaglandins • sodium • heme oxygenase • heme • carbon monoxide

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