PMID- 19249315
OWN - NLM
STAT- MEDLINE
DCOM- 20090528
LR  - 20131121
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 84
IP  - 21-22
DP  - 2009 May 22
TI  - Enhanced vascular contractility in alpha1-adrenergic receptor-deficient mice.
PG  - 713-8
LID - 10.1016/j.lfs.2009.02.020 [doi]
AB  - AIM: 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. MAIN METHODS: The contractile responses to the stimulation with 
      vasoconstrictors were studied using isolated thoracic aorta. KEY FINDINGS: 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. SIGNIFICANCE: 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).
FAU - Sanbe, Atsushi
AU  - Sanbe A
AD  - 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
FAU - Tanaka, Yoshio
AU  - Tanaka Y
FAU - Fujiwara, Yoko
AU  - Fujiwara Y
FAU - Miyauchi, Noriko
AU  - Miyauchi N
FAU - Mizutani, Reiko
AU  - Mizutani R
FAU - Yamauchi, Junji
AU  - Yamauchi J
FAU - Cotecchia, Susanna
AU  - Cotecchia S
FAU - Koike, Katsuo
AU  - Koike K
FAU - Tsujimoto, Gozoh
AU  - Tsujimoto G
FAU - Tanoue, Akito
AU  - Tanoue A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090226
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Receptors, Adrenergic, alpha-1)
RN  - 0 (Vasoconstrictor Agents)
RN  - 333DO1RDJY (Serotonin)
RN  - B7IN85G1HY (Dinoprost)
SB  - IM
MH  - Animals
MH  - Aorta, Thoracic/drug effects
MH  - Blood Pressure/drug effects
MH  - Blotting, Western
MH  - Dinoprost/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression/physiology
MH  - Gene Targeting
MH  - Heart Rate/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Muscle Contraction/*genetics/*physiology
MH  - Muscle, Smooth, Vascular/*physiology
MH  - Receptors, Adrenergic, alpha-1/*genetics/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Serotonin/pharmacology
MH  - Vasoconstrictor Agents/pharmacology
EDAT- 2009/03/03 09:00
MHDA- 2009/05/29 09:00
CRDT- 2009/03/03 09:00
PHST- 2008/09/01 00:00 [received]
PHST- 2009/01/28 00:00 [revised]
PHST- 2009/02/12 00:00 [accepted]
PHST- 2009/03/03 09:00 [entrez]
PHST- 2009/03/03 09:00 [pubmed]
PHST- 2009/05/29 09:00 [medline]
AID - S0024-3205(09)00093-9 [pii]
AID - 10.1016/j.lfs.2009.02.020 [doi]
PST - ppublish
SO  - Life Sci. 2009 May 22;84(21-22):713-8. doi: 10.1016/j.lfs.2009.02.020. Epub 2009 
      Feb 26.