Enhanced vascular contractility in alpha1-adrenergic receptor-deficient mice

AimAlpha1-adrenergic receptors (α1-ARs) are classified into three subtypes: α1A-AR, α1B-AR, and α1D-AR. Triple disruption of α1A-AR, α1B-AR, and α1D-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 (PGF2α) and 5-hydroxytryptamine (5-HT), in α1A-AR, α1B-AR, and α1D-AR triple knockout (α1-AR triple KO) mice.Main methodsThe contractile responses to the stimulation with vasoconstrictors were studied using isolated thoracic aorta.Key findingsAs a result, the phasic and tonic contraction induced by a high concentration of potassium (20 mM) was enhanced in the isolated thoracic aorta of α1-AR triple KO mice compared with that of wild-type (WT) mice. In addition, vascular responses to PGF2α and 5-HT were also enhanced in the isolated thoracic aorta of α1-AR triple KO mice compared with WT mice. Similar to in vitro findings with isolated thoracic aorta, in vivo pressor responses to PGF2α were enhanced in α1-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-HT2A) receptor was up-regulated in the thoracic aorta of α1-AR triple KO mice while the prostaglandin F2α receptor (FP) was unchanged.SignificanceThese results suggest that loss of α1-ARs can lead to enhancement of vascular responsiveness to the vasoconstrictors and may imply that α1-ARs and the subsequent signaling regulate the vascular responsiveness to other stimulations such as depolarization, 5-HT and PGF2α.