Enhanced vascular contractility in alpha1-adrenergic receptor-deficient mice

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Aim Alpha1-adrenergic receptors (α 1-ARs) are classified into three subtypes: α 1A-AR, α 1B-AR, and α 1D-AR. Triple disruption of α 1A-AR, α 1B-AR, and α 1D-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 2α) and 5-hydroxytryptamine (5-HT), in α 1A-AR, α 1B-AR, and α 1D-AR triple knockout (α 1-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 α 1-AR triple KO mice compared with that of wild-type (WT) mice. In addition, vascular responses to PGF 2α and 5-HT were also enhanced in the isolated thoracic aorta of α 1-AR triple KO mice compared with WT mice. Similar to in vitro findings with isolated thoracic aorta, in vivo pressor responses to PGF 2α were enhanced in α 1-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 α 1-AR triple KO mice while the prostaglandin F2α receptor (FP) was unchanged. Significance These results suggest that loss of α 1-ARs can lead to enhancement of vascular responsiveness to the vasoconstrictors and may imply that α 1-ARs and the subsequent signaling regulate the vascular responsiveness to other stimulations such as depolarization, 5-HT and PGF 2α.