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 micromol) 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 nmolkg(-1)min(-1)) for 30min. 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.
Ryan
Michael J
MJ
Department of Physiology & Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216, USA.
Jernigan
Nikki L
NL
Drummond
Heather A
HA
McLemore
Gerald R
GR
Rimoldi
John M
JM
Poreddy
Sambasiva R
SR
Gadepalli
Rama S V
RS
Stec
David E
DE
D000818:Animals; D001880:Boranes / Q000494:pharmacology*; D002248:Carbon Monoxide / Q000378:metabolism; D002254:Carbonates / Q000494:pharmacology*; D002263:Carboxyhemoglobin / Q000032:analysis; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010069:Oxadiazoles / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
C494582:1H-(1,2,3)oxadiazolo(4,4-a)quinoxalin-1-one; D001880:Boranes; D002254:Carbonates; D010069:Oxadiazoles; D024681:Potassium Channels, Calcium-Activated; D011810:Quinoxalines; C503854:sodium boranocarbonate; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin; D006162:Guanylate Cyclase