title: Diabetes-associated alterations in volatile anesthetic actions on contractile response to norepinephrine in isolated mesenteric resistance arteries.
abstract: BACKGROUND
  Clinical concentrations of volatile anesthetics significantly influence contractile response to the sympathetic neurotransmitter norepinephrine although its precise mechanisms remain unclarified. In this study, we investigated its possible alterations in diabetes, as well as its underlying mechanisms.
  
  
  METHODS
  Isometric force was recorded in small mesenteric arteries from streptozotocin-induced diabetic and age-matched control rats.
  
  
  RESULTS
  The concentration-response curve for acetylcholine-induced endothelium-dependent relaxation was shifted to the right in diabetic arteries compared with controls. The concentration-response curve for norepinephrine-induced contraction was shifted to the left and upward by both endothelial denudation and diabetic induction. In the presence of endothelium, isoflurane or sevoflurane enhanced norepinephrine-induced contraction in control arteries but not in diabetic arteries; however, in its absence, both anesthetics identically inhibited norepinephrine-induced contraction in both groups. In control arteries, the isoflurane- or sevoflurane-induced enhancement was not affected by adrenomedullin22-52, calcitonin gene-related peptide8-37, 18beta-glycyrrhetinic acid, N-nitro l-arginine, ouabain, Ba, indomethacin, losartan, ketanserin, BQ-123, and BQ-788.
  
  
  CONCLUSIONS
  In diabetes, vascular responses to acetylcholine, norepinephrine, and volatile anesthetics are altered in mesenteric resistance arteries, presumably reflecting endothelial dysfunction and possibly underlying circulatory instability during administration of either anesthetic. Some endothelial mechanisms that are impaired in diabetes would be involved in the anesthetic-induced enhancement of norepinephrine-induced contraction. However, the vasoregulatory mechanism mediated by adrenomedullin, calcitonin gene-related peptide, myoendothelial gap junction, nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, angiotensin II, serotonin, or endothelin-1, all of which have been suggested to be impaired in diabetes, would not be involved in the enhancement.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshino
authors.forename: Takashi
authors.initials: T
authors.lastname: Akata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shirozu
authors.forename: Kaoru
authors.initials: K
authors.lastname: Izumi
authors.forename: Sumio
authors.initials: S
authors.lastname: Hoka
mesh_terms: D053607:Adrenomedullin / Q000502:physiology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001685:Biological Factors / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D016232:Endothelins / Q000502:physiology; D017629:Gap Junctions / Q000502:physiology; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology; D000077149:Sevoflurane; D013152:Splanchnic Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D001685:Biological Factors; D016232:Endothelins; D008738:Methyl Ethers; D014662:Vasoconstrictor Agents; C067410:endothelium-dependent hyperpolarization factor; D000804:Angiotensin II; D053607:Adrenomedullin; D009569:Nitric Oxide; D012701:Serotonin; D000077149:Sevoflurane; D007530:Isoflurane; D011451:Prostaglandin-Endoperoxide Synthases; D015740:Calcitonin Gene-Related Peptide; D009638:Norepinephrine