Isoflurane and halothane attenuate endothelium-dependent vasodilation in rat coronary microvessels.
Volatile anesthetics attenuate endothelium-dependent vasodilation but the mechanism of attenuation remains controversial. The present study examines the mechanism of isoflurane- and halothane-mediated attenuation of endothelium-dependent vasodilation in Wistar rat coronary microvessels of about 100 microns internal diameter. The vessels were studied in vitro in a pressurized (40 mm Hg), no-flow state using video microscopy. After preconstriction of the vessels with the thromboxane analog U46619 1 microM, concentration response curves to acetylcholine (ACh), the calcium ionophore A23187, sodium nitroprusside (SNP), or the stable cyclic guanosine monophosphate (cGMP) analog 8-bromo-cGMP (Br-cGMP) were obtained in the presence of 0% (control), 1% or 2% isoflurane, or 1% or 2% halothane. Isoflurane 1% and 2% significantly attenuated vasodilation to ACh and A23187. Isoflurane 2%, but not 1%, attenuated vasodilation to SNP. Vasodilation to Br-cGMP was not affected by isoflurane. Halothane attenuated vasodilation to ACh, but had no effect on vasodilation to A23187, SNP, or Br-cGMP. We conclude that isoflurane attenuates endothelium-dependent vasodilation by impairing at least two distinct steps in the nitric oxide (NO)-cGMP pathway, the first being between endothelial increase of calcium and smooth muscle guanylate cyclase and the second being inhibition of soluble guanylate cyclase activity. These two steps appear to have different sensitivities to the effect of isoflurane. Halothane has an effect at the endothelial receptor level, but not any distal steps in the NO-cGMP pathway.
Park
K W
KW
Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Dai
H B
HB
Lowenstein
E
E
Darvish
A
A
Sellke
F W
FW
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000502:physiology; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology*; D008833:Microcirculation / Q000187:drug effects; D018715:Microscopy, Video; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D007476:Ionophores; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; D000001:Calcimycin; D007530:Isoflurane; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D002118:Calcium; D006221:Halothane; D007213:Indomethacin