TY - JOUR
T1 - Cardiovascular influences of α1b-adrenergic receptor defect in mice
AU - Vecchione, Carmine
AU - Fratta, Luigi
AU - Rizzoni, Damiano
AU - Notte, Antonella
AU - Poulet, Roberta
AU - Porteri, Enzo
AU - Frati, Giacomo
AU - Guelfi, Daniele
AU - Trimarco, Valentina
AU - Mulvany, Michael J.
AU - Agabiti-Rosei, Enrico
AU - Trimarco, Bruno
AU - Cotecchia, Susanna
AU - Lembo, Giuseppe
PY - 2002/4/9
Y1 - 2002/4/9
N2 - Background - The α1-adrenergic receptors (α1-ARs) play a key role in cardiovascular homeostasis. However, the functional role of α1-AR subtypes in vivo is still unclear. The aim of this study was to evaluate the cardiovascular influences of α1b-AR. Methods and Results - In transgenic mice lacking α1-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 α1b-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.
AB - Background - The α1-adrenergic receptors (α1-ARs) play a key role in cardiovascular homeostasis. However, the functional role of α1-AR subtypes in vivo is still unclear. The aim of this study was to evaluate the cardiovascular influences of α1b-AR. Methods and Results - In transgenic mice lacking α1-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 α1b-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.
KW - Norepinephrine
KW - Receptors, adrenergic, alpha
KW - Remodeling
UR - http://www.scopus.com/inward/record.url?scp=0037046072&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037046072&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.0000012750.08480.55
DO - 10.1161/01.CIR.0000012750.08480.55
M3 - Article
C2 - 11940550
AN - SCOPUS:0037046072
VL - 105
SP - 1700
EP - 1707
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 14
ER -