The α1D-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction

Subtypes of functional α1-adrenoceptor

“…In studies of mouse carotid artery from WT and alpha1D-KO, there was evidence for predominantly a1D-adrenoceptormediated contractions with some regulatory role for the a1B-adrenoceptor [96]. Mouse aortic contractions to noradrenaline and phenylephrine were unaffected by a1B-KO [89], markedly reduced by a1D-KO [89,97], but abolished by combination of a1B/1D-KO [89], suggesting a regulatory or co-operative role for a1B-adrenoceptors. However, overexpression of a1B-adrenoceptors did not affect the a1D-adrenoceptor response of mouse aorta [98] or mesenteric artery [92].…”

“…However, in a1A/a1B double knockout mice, there was no significant fall in blood pressure [129]. In mice lacking the alpha1D-adrenoceptor, or both a1D and a1B, there was a significant fall in resting blood pressure both by tail cuff and invasive recording, and a small fall in the pressor response both to phenylephrine and noradrenaline [89,97]. Of note in Table 2 are several facts.…”

“…b3-Adrenoceptors have also been implicated in thermogenesis [133], but b3-adrenoceptor ligands have been associated with a1-adrenoceptor antagonism, and some of the actions may involve alpha1-adrenoceptors [59,134]. Phe pressor No change [128] Decrease [88] Small decrease [97] No change [89] No change [89] 1B/1D double KO: decrease [89] NA pressor Small decrease [88] Small decrease [97] Small decrease [89] Decrease [89] 1B/1D double KO: decrease [89] Results taken from [88,89,97,128,129] SBP systolic blood pressure (recorded by tail cuff), HR heart rate, MAP mean arterial pressure (recorded by invasive cannula), phe pressor pressor response to phenylephrine relative to WT, NA pressor pressor response to noradrenaline relative to WT *Significant difference from respective WT a1-adrenoceptor subtypes Peripheral effects of MDMA at a1-adrenoceptors can explain a component of the hyperthermia: cutaneous vasoconstriction by MDMA prevents an early hypothermic response to the drug. At low ambient temperatures, cutaneous vasoconstriction is already marked so that MDMA produces little further vasoconstriction and the, presumed central, hypothermic actions of MDMA may predominate.…”

The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions

“…DNA fragments of 2.5 kb and 6.0 kb were subcloned from the mouse V1b receptor genomic clone ( Figure 1) into pBluescript (Stratagene, La Jolla, California, USA). These two fragments were inserted into a plasmid with a 1.6-kb cassette containing the neomycin resistance gene (Neo) under the control of the phosphoglycerate kinase promoter, as described (17). As a result, the 3.5-kb region including the first exon and part of the first intron of the V1b receptor gene was replaced with the Neo cassette.…”

“…RNA preparation and RT-PCR were performed as described previously (17). Thermal cycling was performed for 30 seconds at 94°C, 30 seconds at 57°C, and 2 minutes at 72°C for 30 cycles.…”