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Am J Physiol Renal Physiol 295: F904-F911, 2008. First published July 16, 2008; doi:10.1152/ajprenal.90377.2008
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EDITORIAL FOCUS

Heme oxygenase induction attenuates afferent arteriolar autoregulatory responses

Fady T. Botros, Minolfa C. Prieto-Carrasquero, Victoria L. Martin, and L. Gabriel Navar

Department of Physiology, Hypertension and Renal Center, Tulane University Health Sciences Center, New Orleans, Louisiana

Submitted 19 June 2008 ; accepted in final form 15 July 2008

Heme oxygenases (HO-1, HO-2) catalyze conversion of heme to iron, carbon monoxide (CO), and biliverdin/bilirubin. We studied the effects of renal HO-1 induction on afferent arteriole (Aff-Art) autoregulatory responses to increases in renal perfusion pressure (RPP). Rats were treated with hemin and SnCl2 to induce HO-1, and Aff-Art autoregulatory responses were evaluated using the rat blood-perfused juxtamedullary nephron preparation. Renal HO-1 expression was significantly increased in hemin- and SnCl2-treated rats, while HO-2 was not altered. Aff-Art autoregulatory constrictor responses to increases in RPP from 100 to 150 mmHg were attenuated in hemin- and SnCl2-treated rats compared with control rats (+1.1 ± 3.3, n = 9 and +4.4 ± 5.3, n = 9 vs. –14.2 ± 1.5%, n = 10, respectively) (P < 0.05). Acute HO inhibition with chromium mesoporphyrin (CrMP; 15 µmol/l) restored Aff-Art autoregulatory responses in hemin- and SnCl2-treated rats. Superfusing Aff-Arts from control rats with 100 µmol/l biliverdin did not alter autoregulatory responses; however, superfusion with 1 mmol/l CO significantly attenuated autoregulatory responses to increases in RPP from 100 to 150 mmHg (+3.3 ± 5.4 vs. –16.6 ± 3.8%, n = 6) (P < 0.05). Acute soluble guanylate cyclase inhibition with 10 µmol/l ODQ restored Aff-Art autoregulatory responses in hemin-treated rats. Immunohistochemistry shows HO-2 to be expressed mainly in epithelial cells with weak staining in proximal tubules, interlobular arteries, and Aff-Arts. In hemin- and SnCl2-treated rats, HO-1 was induced in tubular epithelial cells but not interlobular arteries and Aff-Arts. We conclude that induction of renal HO-1 attenuates Aff-Art constrictor responses to increases in RPP via increasing CO production from tubular epithelial cells, suggesting that an augmented HO system in pathophysiological conditions modulates renal autoregulation.

hemin; carbon monoxide; biliverdin; bilirubin; autoregulation; kidney; tin chloride; soluble guanylate cyclase



Address for reprint requests and other correspondence: F. T. Botros, Dept. of Physiology, Hypertension and Renal Center, Tulane Univ. Health Sciences Center, 1430 Tulane Ave., SL39, New Orleans, LA 70112 (e-mail: fbotros{at}tulane.edu)







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