Dilation by isoflurane of preconstricted, very small arterioles from human right atrium is mediated in part by K(+)-ATP channel opening.
The adenosine triphosphate (ATP)-sensitive potassium channels (K(+)-ATP channels) are activated by decreases in intracellular ATP and help to match blood flow to tissue needs. Such metabolism-flow coupling occurs predominantly in the smallest arterioles measuring 50 microm or less in diameter. Previous studies demonstrated that isoflurane may activate the K(+)-ATP channels in larger arteries. We examined whether isoflurane also activates the channels in the smallest arterioles of approximately 50 microm. Microvessels of approximately 50 microm were dissected from right atrial appendages from patients undergoing coronary artery bypass surgery and were monitored in vitro for diameter changes by videomicroscopy. With or without preconstriction with the thromboxane analog U46619 1 microM, vessels were exposed to isoflurane 0%-3% either in the presence or absence of the K(+)-ATP channel blocker glibenclamide 1 microM. Without preconstriction, isoflurane neither dilated nor constricted the vessels significantly. After preconstriction, isoflurane had a concentration-dependent dilation of the small arterioles (39 +/- 13% [mean +/- SD] dilation at 3% isoflurane) (P < 0.001), and this effect was significantly attenuated by glibenclamide (18 +/- 5% dilation at 3% isoflurane) (P < 0.01). In comparison, nitroprusside 10(-4) M produced 79 +/- 6% dilation, and adenosine diphosphate 10(-4) M produced 29 +/- 7% dilation. We conclude that isoflurane-mediated dilation of the smallest resistance arterioles may be in part based on activation of the K(+)-ATP channels when the arterioles are relatively constricted.


CONCLUSIONS
Vasodilation of very small coronary arterioles by isoflurane depends on preexisting tone and may in part be mediated by the K(+)-ATP channels.
Park
K W
KW
Departments of Anesthesia and Critical Care and Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. kpark@caregroup.harvard.edu
Dai
H B
HB
Comunale
M E
ME
Gopal
A
A
Sellke
F W
FW
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D020517:Atrial Appendage; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D007530:Isoflurane