Anesthetics alter relative contributions of NO and EDHF in rat cremaster muscle microcirculation.
The contributions of the vasodilators nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) were investigated in the rat cremaster muscle microcirculation during halothane, isoflurane, or ketamine anesthesia. After inhibition of prostaglandin synthesis with indomethacin, changes in diameter of fourth-order arterioles to acetylcholine (ACh) or bradykinin (BK) were studied in the presence or absence of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, and/or 20 mM K+, an inhibitor of EDHF action. L-NMMA inhibited ACh- and BK-induced vasodilation during isoflurane but not halothane or ketamine anesthesia. Superfusion of the muscle with buffer containing 20 mM K+ dilated arterioles. EDHF was responsible for most of the NO-independent response to ACh, because 20 mM K+ unmasked ACh-stimulated, NO-dependent relaxation during halothane or ketamine anesthesia. However, 20 mM K+ did not inhibit BK-induced vasodilation during halothane or ketamine anesthesia. Our data suggest that anesthetics can alter the balance between NO and EDHF vasodilation in the microcirculation and that NO-dependent mechanisms are enhanced and EDHF action inhibited during isoflurane anesthesia.
Loeb
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Department of Anesthesia, University of Pennsylvania, Philadelphia 19104-4283, USA.
Gödény
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Longnecker
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D000009:Abdominal Muscles / Q000098:blood supply*; D000777:Anesthetics / Q000494:pharmacology*; D000778:Anesthetics, Dissociative / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D006221:Halothane / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D000777:Anesthetics; D000778:Anesthetics, Dissociative; D018685:Anesthetics, Inhalation; D001685:Biological Factors; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D007649:Ketamine; D007530:Isoflurane; D006221:Halothane