The alpha(1D)-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction.
To investigate the physiological role of the alpha(1D)-adrenergic receptor (alpha(1D)-AR) subtype, we created mice lacking the alpha(1D)-AR (alpha(1D)(-/-)) by gene targeting and characterized their cardiovascular function. In alpha(1D)-/- mice, the RT-PCR did not detect any transcript of the alpha(1D)-AR in any tissue examined, and there was no apparent upregulation of other alpha(1)-AR subtypes. Radioligand binding studies showed that alpha(1)-AR binding capacity in the aorta was lost, while that in the heart was unaltered in alpha(1D)-/- mice. Non-anesthetized alpha(1D)-/- mice maintained significantly lower basal systolic and mean arterial blood pressure conditions, relative to wild-type mice, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. Besides hypotension, the pressor responses to phenylephrine and norepinephrine were decreased by 30-40% in alpha(1D)-/- mice. Furthermore, the contractile response of the aorta and the pressor response of isolated perfused mesenteric arterial beds to alpha(1)-AR stimulation were markedly reduced in alpha(1D)-/- mice. We conclude that the alpha(1D)-AR participates directly in sympathetic regulation of systemic blood pressure by vasoconstriction.
Tanoue
Akito
A
Department of Molecular, Cell Pharmacology, National Children's Medical Research Center, 3-35-31 Taishido, Setagaya-ku, Tokyo, 154-8509 Japan.
Nasa
Yoshihisa
Y
Koshimizu
Takaaki
T
Shinoura
Hitomi
H
Oshikawa
Sayuri
S
Kawai
Takayuki
T
Sunada
Sachie
S
Takeo
Satoshi
S
Tsujimoto
Gozoh
G
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology*; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018390:Gene Targeting; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D014020:Tissue Extracts / Q000378:metabolism; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology
C547720:Adra1d protein, mouse; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D011799:Quinazolines; D018340:Receptors, Adrenergic, alpha-1; D014020:Tissue Extracts; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D000804:Angiotensin II; D010656:Phenylephrine; D012701:Serotonin; C018176:bunazosin; C053428:BMY 7378; D009638:Norepinephrine