Isoflurane attenuates cAMP-mediated vasodilation in rat microvessels.
BACKGROUND
Endothelium-dependent vasodilation mediated by cGMP is known to be attenuated by the inhalational anesthetic isoflurane. The present study examines the effect of isoflurane on beta-adrenergic and cAMP-mediated vasodilation.


RESULTS
Fifty-three subepicardial coronary arteries (diameter, 103 +/- 13 microns) from Wistar rats were studied in vitro in a pressurized (40 mm Hg), no-flow state with use of optical density video detection system. After preconstriction of vessels with the thromboxane A2 analogue U46619 10(-6) mol/L, concentration response curves to the nonselective beta-adrenergic agonist isoproterenol, the Gs protein activator sodium fluoride, the adenylate cyclase activator forskolin, the cAMP analogue 8-Br-cAMP, or the phosphodiesterase inhibitor RO20-1724 were obtained either in the presence of absence (control) of 2% isoflurane. Relaxations to all the agents tested were significantly reduced in the presence of isoflurane compared with controls.


CONCLUSIONS
Isoflurane attenuates cAMP-mediated vasodilation. The impairment appears to be distal to adenylate cyclase and is not due to enhancement of cAMP phosphodiesterase.
Park
K W
KW
Department of Anesthesia and Critical Care, Beth Israel Hospital, Harvard Medical School, Boston, MA 02215, USA.
Dai
H B
HB
Lowenstein
E
E
Darvish
A
A
Sellke
F W
FW
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D005260:Female; D007530:Isoflurane / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D000318:Adrenergic beta-Agonists; D007530:Isoflurane; D000242:Cyclic AMP; D007545:Isoproterenol