Heme oxygenase induction attenuates afferent arteriolar autoregulatory responses

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 mu mol/l) restored Aff-Art autoregulatory responses in hemin-and SnCl2-treated rats. Superfusing Aff-Arts from control rats with 100 mu mol/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 mu mol/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.