Renal vascular responses to CORM-A1 in the mouse

CORM-A1 is a newly described water-soluble carbon monoxide (CO) releasing molecule (CORM) that can deliver CO to various vascular beds in the absence of dramatic changes in blood carboxy-hemoglobin (COHb) levels. We tested the in vivo and in vitro renal vascular effects of CORM-A1 administration using anesthetized mice instrumented with a renal flow probe as well as in isolated, pressurized renal interlobar arteries. Administration of CORM-A1 (0.96 μmol) resulted in a significant increase in renal blood flow (RBF) of 33 ± 6% as compared to control. Administration of acetylcholine (50 pmol) caused a similar increase in RBF (25 ± 4%). In order to determine if the vasodilatory effect of CORM-A1 in vivo was mediated through activation of soluble guanylate cyclase (sGC), mice were pretreated with the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 nmol kg−1 min−1) for 30 min. Pretreatment with ODQ significantly reduced the CORM-A1 mediated increase in RBF to 9 ± 5% of control. In isolated pressurized renal interlobar arteries, CORM-A1 caused dose dependent vasodilatation of phenylephrine constricted arteries. The CORM-A1 mediated vasodilatation was significantly attenuated by ODQ to similar levels as observed in vivo. Inhibition of calcium activated potassium channels (Kca) with iberiotoxin resulted in a complete blockade of the CORM-A1 mediated vasodilatation in pressurized renal interlobar arteries. We conclude that CO released from CORM-A1 causes an increase in RBF and a decrease in vascular resistance through activation of sGC and opening of Kca channels in the kidney of the mouse.