Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

Heme oxygenases (HO-1; HO-2) catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n = 7) and hemintreated rats (n = 6) were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF) was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115 +/- 5 mmHg versus 112 +/- 4 mmHg and 331 +/- 16 versus 346 +/- 10 bpm). However, RBF was significantly higher (9.1 +/- 0.8 versus 7.0 +/- 0.5 mL/min/g, P < 0.05), and renal vascular resistance was significantly lower (13.0 +/- 0.9 versus 16.6 +/- 1.4 [mmHg/(mL/min/g)], P < 0.05). Likewise, glomerular filtration rate was significantly elevated (1.4 +/- 0.2 versus 1.0 +/- 0.1 mL/min/g, P < 0.05), and urine flow and sodium excretion were also higher (18.9 +/- 3.9 versus 8.2 +/- 1.0 mu L/min/g, P < 0.05 and 1.9 +/- 0.6 versus 0.2 +/- 0.1 mu mol/min/g, P < 0.05, resp.). The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models.