title: Endothelium-dependent pulmonary vasodilation is selectively attenuated during isoflurane anesthesia.
abstract: We have recently reported that halothane (Hal) anesthesia attenuates the pulmonary vasodilator responses to both bradykinin (BK) and sodium nitroprusside (SNP) compared with responses measured in the conscious state. These agonists have been classically used to activate endothelium-dependent and -independent vasodilator pathways, respectively. Our present goal was to assess the effect of isoflurane (Iso) anesthesia on pulmonary vasodilation activated via these pathways. Left pulmonary vascular pressure-flow (P-Q) plots were used to measure the pulmonary vascular responses to cumulative intravenous doses of BK, SNP, and 3-morpholinosydonimine-N-ethylcarbamide (SIN-1), a nitric oxide donor, in chronically instrumented dogs in the conscious state and during Iso anesthesia after matched preconstriction with the thromboxane analogue U-46619. Iso attenuated the vasodilator response to BK (P < 0.05). However, Iso had a differential effect on the responses to SIN-1 and SNP. Iso potentiated the vasodilator response to SIN-1 (P < 0.05), whereas Iso attenuated the response to SNP (P < 0.05). The vasodilator response to SIN-1 was unchanged during Hal anesthesia. The ATP-sensitive potassium (KATP)-channel inhibitor glibenclamide attenuated the vasodilator response to SNP (P < 0.05) but not to SIN-1. Thus Iso and Hal selectively attenuate the endothelium-dependent pulmonary vasodilator response to BK. Both anesthetics attenuate vasodilation induced by SNP but not by SIN-1. Moreover, a component of SNP-induced vasodilation involves KATP-channel activation.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Gambone
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: P A
authors.initials: PA
authors.lastname: Murray
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005740:Gases / Q000097:blood; D006221:Halothane; D006439:Hemodynamics; D006706:Homeostasis; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D005740:Gases; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D013928:Thromboxane A2; C002385:linsidomine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007530:Isoflurane; D008981:Molsidomine; D001920:Bradykinin; D006221:Halothane