title: Adaptation of the hypothalamic blood flow to chronic nitric oxide deficiency is independent of vasodilator prostanoids.
abstract: The aim of our study was to investigate the adaptation of the hypothalamic circulation to chronic nitric oxide (NO) deficiency in rats. Hypothalamic blood flow (HBF) remained unaltered during chronic oral administration of the NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME, 1 mg/ml drinking water) although acute NOS blockade by intravenous l-NAME injection (50 mg/kg) induced a dramatic HBF decrease. In chronically NOS blocked animals, however, acute l-NAME administration failed to influence the HBF. Reversal of chronic NOS blockade by intravenous l-arginine infusion evoked significant hypothalamic hyperemia suggesting the appearance of a compensatory vasodilator mechanism in the absence of NO. In order to clarify the potential involvement of vasodilator prostanoids in this adaptation, cyclooxygenase (COX) mRNA and protein levels were determined in the hypothalamus, but none of the known isoenzymes (COX-1, COX-2, COX-3) showed upregulation after chronic NOS blockade. Furthermore, levels of vasodilator prostanoid (PGI(2), PGE(2) and PGD(2)) metabolites were also not elevated. Interestingly, however, hypothalamic levels of vasoconstrictor prostanoids (TXA(2) and PGF(2alpha)) decreased after chronic NOS blockade. COX inhibition by indomethacin but not by diclofenac decreased the HBF in control animals. However, neither indomethacin nor diclofenac induced an altered HBF-response after chronic l-NAME treatment. Although urinary excretion of PGI(2) and PGE(2) metabolites markedly increased during chronic NOS blockade, indicating COX activation in the systemic circulation, we conclude that the adaptation of the hypothalamic circulation to the reduction of NO synthesis is independent of vasodilator prostanoids. Reduced release of vasoconstrictor prostanoids, however, may contribute to the normalization of HBF after chronic loss of NO.
authors.affiliation: Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Hortobágyi
authors.forename: Béla
authors.initials: B
authors.lastname: Kis
authors.forename: András
authors.initials: A
authors.lastname: Hrabák
authors.forename: Béla
authors.initials: B
authors.lastname: Horváth
authors.forename: Gergely
authors.initials: G
authors.lastname: Huszty
authors.forename: Horst
authors.initials: H
authors.lastname: Schweer
authors.forename: Balázs
authors.initials: B
authors.lastname: Benyó
authors.forename: Péter
authors.initials: P
authors.lastname: Sándor
authors.forename: David W
authors.initials: DW
authors.lastname: Busija
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Benyó
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D002941:Circle of Willis / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism; D006940:Hyperemia / Q000139:chemically induced; D007031:Hypothalamus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000172:deficiency*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015230:Prostaglandin D2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D014665:Vasodilator Agents; D009569:Nitric Oxide; D001120:Arginine; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D015230:Prostaglandin D2