Carbon monoxide of vascular origin attenuates the sensitivity of renal arterial vessels to vasoconstrictors.
Rat renal interlobar arteries express heme oxygenase 2 (HO-2) and manufacture carbon monoxide (CO), which is released into the headspace gas. CO release falls to 30% and 54% of control, respectively, after inhibition of HO activity with chromium mesoporphyrin (CrMP) or of HO-2 expression with antisense oligodeoxynucleotides (HO-2 AS-ODN). Patch-clamp studies revealed that CrMP decreases the open probability of a tetraethylammonium-sensitive (TEA-sensitive) 105 pS K channel in interlobar artery smooth muscle cells, and that this effect of CrMP is reversed by CO. Assessment of phenylephrine-induced tension development revealed reduction of the EC(50) in vessels treated with HO-2 AS-ODN, CrMP, or TEA. Exogenous CO greatly minimized the sensitizing effect on agonist-induced contractions of agents that decrease vascular CO production, but not the sensitizing effect of K channel blockade with TEA. Collectively, these data suggest that vascular CO serves as an inhibitory modulator of vascular reactivity to vasoconstrictors via a mechanism that involves a TEA-sensitive K channel.
Kaide
J I
JI
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA. Jun-Ichi_Kaide@nymc.edu
Zhang
F
F
Wei
Y
Y
Jiang
H
H
Yu
C
C
Wang
W H
WH
Balazy
M
M
Abraham
N G
NG
Nasjletti
A
A
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D002248:Carbon Monoxide / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008652:Mesoporphyrins / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology
D008652:Mesoporphyrins; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D014662:Vasoconstrictor Agents; C427471:chromium mesoporphyrin; D014667:Vasopressins; D010656:Phenylephrine; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; C027917:tetramethylammonium