title: Enhanced vascular contractility in alpha1-adrenergic receptor-deficient mice.
abstract: OBJECTIVE
  Alpha1-adrenergic receptors (alpha1-ARs) are classified into three subtypes: alpha1A-AR, alpha1B-AR, and alpha1D-AR. Triple disruption of alpha1A-AR, alpha1B-AR, and alpha1D-AR genes results in hypotension and produces no contractile response of the thoracic aorta to noradrenalin. Presently, we characterized vascular contractility against other vasoconstrictors, such as potassium, prostaglandin F2alpha (PGF(2alpha)) and 5-hydroxytryptamine (5-HT), in alpha1A-AR, alpha1B-AR, and alpha1D-AR triple knockout (alpha1-AR triple KO) mice.
  
  
  METHODS
  The contractile responses to the stimulation with vasoconstrictors were studied using isolated thoracic aorta.
  
  
  RESULTS
  As a result, the phasic and tonic contraction induced by a high concentration of potassium (20 mM) was enhanced in the isolated thoracic aorta of alpha1-AR triple KO mice compared with that of wild-type (WT) mice. In addition, vascular responses to PGF(2alpha) and 5-HT were also enhanced in the isolated thoracic aorta of alpha1-AR triple KO mice compared with WT mice. Similar to in vitro findings with isolated thoracic aorta, in vivo pressor responses to PGF(2alpha) were enhanced in alpha1-AR triple KO mice. Real-time reverse transcription-polymerase chain reaction analysis and western blot analysis indicate that gene expression of the 5-hydroxytryptamine 2A (5-HT(2A)) receptor was up-regulated in the thoracic aorta of alpha1-AR triple KO mice while the prostaglandin F2alpha receptor (FP) was unchanged.
  
  
  CONCLUSIONS
  These results suggest that loss of alpha1-ARs can lead to enhancement of vascular responsiveness to the vasoconstrictors and may imply that alpha1-ARs and the subsequent signaling regulate the vascular responsiveness to other stimulations such as depolarization, 5-HT and PGF(2alpha).
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan. asanbe@nch.go.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sanbe
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyauchi
authors.forename: Reiko
authors.initials: R
authors.lastname: Mizutani
authors.forename: Junji
authors.initials: J
authors.lastname: Yamauchi
authors.forename: Susanna
authors.initials: S
authors.lastname: Cotecchia
authors.forename: Katsuo
authors.initials: K
authors.lastname: Koike
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000502:physiology; D018390:Gene Targeting; D006339:Heart Rate / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics* / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D012701:Serotonin; D015237:Dinoprost