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 (Aft-Art) autoregulatory responses to increases in renal perfusion pressure (RPP). Rats were treated with hemin and Sn[Cl.sub.2] to induce HO-1, and Aft-Art autoregulatory responses were evaluated using the rat blood-perfused juxtamedullary nephron preparation. Renal HO-1 expression was significantly increased in hemin- and Sn[Cl.sub.2]-treated rats, while HO-2 was not altered. Aft-Art autoregulatory constrictor responses to increases in RPP from 100 to 150 mmHg were attenuated in hemin- and Sn[Cl.sub.2]-treated rats compared with control rats (+ 1.1 [+ or -] 3.3, n = 9 and +4.4 [+ or -] 5.3, n = 9 vs. -14.2 [+ or -] 1.5%, n = 10, respectively) (P < 0.05). Acute HO inhibition with chromium mesoporphyrin (CrMP; 15 [micro]mol/1) restored Aft-Art autoregulatory responses in hemin- and Sn[Cl.sub.2]-treated rats. Superfusing Aff-Arts from control rats with 100 [micro]mol/1 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 [+ or -] 5.4 vs. -16.6 [+ or -] 3.8%, n = 6) (P < 0.05). Acute soluble guanylate cyclase inhibition with 10 [micro]mol/l ODQ restored Aft-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 Aft-Arts. In hemin- and Sn[Cl.sub.2]-treated rats, HO-I was induced in tubular epithelial cells but not interlobular arteries and Aft-Arts. We conclude that induction of renal HO- I attenuates Aft-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