Carbon monoxide produced by isolated arterioles attenuates pressure-induced vasoconstriction.
Studies were conducted on isolated rat gracilis muscle arterioles to examine the role of vascular heme oxygenase (HO)-derived carbon monoxide (CO) on myogenic constrictor responses to stepwise increments in intraluminal pressure. The arterioles express HO-2 but not HO-1 and manufacture CO. Both HO-2 protein expression and CO production are reduced in arterioles maintained for 18 h before experimentation in media containing HO-2 antisense oligodeoxynucleotides (AS-ODN). Pressurization of arterioles mounted on a myograph over the pressure range of 40--100 mmHg elicits reduction of internal diameter. At pressures >40 mmHg, the internal diameter of vessels treated with either HO-2 AS-ODN, the HO inhibitor chromium mesoporphyrin (CrMP), or the K(+) channel blocker tetraethylammonium (TEA) are smaller than the corresponding control values. The inclusion of exogenous CO, but not of biliverdin, in the superfusion buffer attenuates pressure-induced vasoconstriction in CrMP-treated vessels. However, exogenous CO does not attenuate pressure-induced vasoconstriction in vessels treated with both CrMP and TEA. Collectively, these data suggest that CO of vascular origin attenuates pressure-induced arteriolar constriction via a mechanism involving a TEA-sensitive K(+) channel.
Zhang
F
F
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA. Fan_Zhang@nymc.edu
Kaide
J
J
Wei
Y
Y
Jiang
H
H
Yu
C
C
Balazy
M
M
Abraham
N G
NG
Wang
W
W
Nasjletti
A
A
D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology*; D002248:Carbon Monoxide / Q000378:metabolism*; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008652:Mesoporphyrins / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology*
D004791:Enzyme Inhibitors; D008652:Mesoporphyrins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C427471:chromium mesoporphyrin; D019789:Tetraethylammonium; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing)