Submitted on June 19, 2008
Revised on July 15, 2008
Accepted on July 15, 2008
Heme oxygenase induction attenuates afferent arteriolar autoregulatory responses
Fady T. Botros1*, Minolfa C Prieto-Carrasquero2, Victoria L. Martin3, and L. Gabriel Navar4
1 Tulane University
2 Tulane University Health Sciences Center
3 Tulane University HSC
4 Tulane University School of Medicine
* To whom correspondence should be addressed. E-mail: fbotros{at}tulane.edu.
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 to 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, 15µmol/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, superfusing 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.
