Expression and actions of heme oxygenase in the renal medulla of rats

Recent studies have shown that the heme oxygenase (HO) product, carbon mono xide (CO), induces vasodilation and that inhibition of HO produces a sustai ned hypertension in rats. Given the importance of renal medullary blood flo w (MBF) in the long-term control of arterial blood pressure, we hypothesize d that the HO/CO system may play an important role in maintaining the const ancy of blood flow to the renal medulla, which in turn contributes to the a ntihypertensive effects of the renal medulla. To test this hypothesis, we f irst determined the expression of 2 isoforms of HO (HO-1 and HO-2) in the d ifferent kidney regions. By Northern blot analyses, the abundance of both i sozyme mRNAs was found highest in the renal inner medulla and lowest in the renal cortex. The transcripts for HO-1 in the renal outer medulla and inne r medulla were 2.5 and 3.7 times that expressed in the renal cortex and tho se for HO-2 in the outer medulla and inner medulla were 1.3 and 1.6 times t hat expressed in the renal cortex, respectively. Western blot analyses of b oth enzymes showed the same expression pattern in these kidney regions as t he mRNAs. To determine the role that HO plays in the control of renal MBF, we examined the effect of the HO inhibitor zinc deuteroporphyrin 2,4-bis gl ycol (ZnDPBG) on cortical blood flow and MBF in anesthetized rats. ZnDPBG w as given by renal medullary interstitial infusion, and cortical blood Row a nd MBF were measured by laser Doppler flowmetry. Renal medullary interstiti al infusion of ZnDPBG at a dose of 60 nmol/kg per minute produced a 31% dec rease in MBF over a period of 60 minutes as measured by laser Doppler flow signal (0.62+/-0.02 vs 0.43+/-0.04 V in control vs ZnDPBG). With the use of an in vivo microdialysis technique, ZnDPBG was found to significantly redu ce renal medullary cGMP concentrations when infused into the renal medullar y interstitial space. These results suggest that both HO-1 and HO-2 are hig hly expressed in the renal medulla, that HO and its products play an import ant role in maintaining the constancy of blood flow to the renal medulla, a nd that cGMP may mediate the vasodilator effect of HO products in the renal medullary circulation.