Cardiovascular influences of alpha1b-adrenergic receptor defect in mice.
BACKGROUND
The alpha1-adrenergic receptors (alpha1-ARs) play a key role in cardiovascular homeostasis. However, the functional role of alpha1-AR subtypes in vivo is still unclear. The aim of this study was to evaluate the cardiovascular influences of alpha1b-AR.


RESULTS
In transgenic mice lacking alpha1-AR (KO) and their wild-type controls (WT), we evaluated blood pressure profile and cardiovascular remodeling induced by the chronic administration (18 days via osmotic pumps) of norepinephrine, angiotensin II, and subpressor doses of phenylephrine. Our results indicate that norepinephrine induced an increase in blood pressure levels only in WT mice. In contrast, the hypertensive state induced by angiotensin II was comparable between WT and KO mice. Phenylephrine did not modify blood pressure levels in either WT or KO mice. The cardiac hypertrophy and eutrophic vascular remodeling evoked by norepinephrine was observed only in WT mice, and this effect was independent of the hypertensive state because it was similar to that observed during subpressor phenylephrine infusion. Finally, the cardiac hypertrophy induced by thoracic aortic constriction was comparable between WT and KO mice.


CONCLUSIONS
Our data demonstrate that the lack of alpha1b-AR protects from the chronic increase of arterial blood pressure induced by norepinephrine and concomitantly prevents cardiovascular remodeling evoked by adrenergic activation independently of blood pressure levels.
Vecchione
Carmine
C
I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
Fratta
Luigi
L
Rizzoni
Damiano
D
Notte
Antonella
A
Poulet
Roberta
R
Porteri
Enzo
E
Frati
Giacomo
G
Guelfi
Daniele
D
Trimarco
Valentina
V
Mulvany
Michael J
MJ
Agabiti-Rosei
Enrico
E
Trimarco
Bruno
B
Cotecchia
Susanna
S
Lembo
Giuseppe
G
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D006332:Cardiomegaly / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D002319:Cardiovascular System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D004452:Echocardiography; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008643:Mesentery / Q000098:blood supply; D051379:Mice; D008822:Mice, Transgenic; D009638:Norepinephrine / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects / Q000235:genetics; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects / Q000235:genetics
C547717:Adra1b protein, mouse; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D009638:Norepinephrine