title: Mechanisms Underlying Enhanced Noradrenaline-Induced Femoral Arterial Contractions of Spontaneously Hypertensive Rats: Involvement of Endothelium-Derived Factors and Cyclooxygenase-Derived Prostanoids.
abstract: We investigated the relationship between noradrenaline (NAd)-induced contractions, endothelial function, and hypertension in femoral arteries isolated from spontaneously hypertensive rats (SHR). In the femoral arteries of SHR, vs. age-matched control Wistar Kyoto (WKY) rats, contractions induced by NAd were increased. These effects were enhanced by endothelial denudation, which abolished the differences between the two groups. NAd-induced contractions were enhanced by nitric oxide (NO) synthase inhibition, and further increased by the blockade of endothelium-derived hyperpolarizing factor (EDHF). Conversely, NAd-induced contractions were inhibited by cyclooxygenase (COX) inhibition. In addition, in SHR arteries, acetylcholine-induced relaxation was reduced, and components of endothelium-derived factors were altered, such as increased COX-derived vasoconstrictor prostanoids, reduced EDHF, and preserved NO-mediated relaxation. In the femoral arteries of SHR, the production of prostanoids [6-keto prostaglandin (PG)F1α (a metabolite of prostacyclin (PGI2), PGE2, and PGF2α] and COX-2 protein were increased compared with that in WKY rats. By contrast, contractions induced by beraprost (a stable PGI2 analogue), PGE2, and U46619 (thromboxane/prostanoid receptor agonist) were similar between the SHR and WKY groups. Thus, NAd-induced femoral arterial contractions are augmented in SHR resulting from endothelial dysfunction and increased COX-derived vasoconstrictor prostanoid levels.
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Shun
authors.initials: S
authors.lastname: Watanabe
authors.forename: Maika
authors.initials: M
authors.lastname: Iguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Ando
authors.forename: Mirai
authors.initials: M
authors.lastname: Oda
authors.forename: Mako
authors.initials: M
authors.lastname: Nagata
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yamada
authors.forename: Kumiko
authors.initials: K
authors.lastname: Taguchi
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000109:Acetylcholine; D000818:Animals; D001685:Biological Factors / Q000037:antagonists & inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D005263:Femoral Artery / Q000378:metabolism / Q000502:physiology / Q000503:physiopathology*; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine; D011453:Prostaglandins / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents
chemical_list: D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D009638:Norepinephrine