Academic Journal
Enhanced vascular contractility in alpha1-adrenergic receptor-deficient mice.
| Title: | Enhanced vascular contractility in alpha1-adrenergic receptor-deficient mice. |
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| Authors: | Sanbe, A., Tanaka, Y., Fujiwara, Y., Miyauchi, N., Mizutani, R., Yamauchi, J., Cotecchia, S., Koike, K., Tsujimoto, G., Tanoue, A. |
| Publication Year: | 2009 |
| Collection: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| Subject Terms: | Animals, Aorta, Thoracic/drug effects, Blood Pressure/drug effects, Blotting, Western, Dinoprost/pharmacology, Dose-Response Relationship, Drug, Gene Expression/physiology, Gene Targeting, Heart Rate/drug effects, Mice, Inbred C57BL, Knockout, Muscle Contraction/genetics, Muscle Contraction/physiology, Muscle, Smooth, Vascular/physiology, Receptors, Adrenergic, alpha-1/genetics, alpha-1/physiology, Reverse Transcriptase Polymerase Chain Reaction, Serotonin/pharmacology, Vasoconstrictor Agents/pharmacology |
| Description: | 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). |
| Document Type: | article in journal/newspaper |
| Language: | English |
| ISSN: | 1879-0631 |
| Relation: | Life Sciences; https://iris.unil.ch/handle/iris/255361; serval:BIB_FDE2B7FACE6B; 000266281600002 |
| DOI: | 10.1016/j.lfs.2009.02.020 |
| Availability: | https://iris.unil.ch/handle/iris/255361 https://doi.org/10.1016/j.lfs.2009.02.020 |
| Accession Number: | edsbas.5997C2F5 |
| Database: | BASE |
| ISSN: | 18790631 |
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| DOI: | 10.1016/j.lfs.2009.02.020 |