Vecchione Carmine, Fratta Luigi, Rizzoni Damiano, Notte Antonella, Poulet Roberta, Porteri Enzo, Frati Giacomo, Guelfi Daniele, Trimarco Valentina, Mulvany Michael J, Agabiti-Rosei Enrico, Trimarco Bruno, Cotecchia Susanna, Lembo Giuseppe
I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
Circulation. 2002 Apr 9;105(14):1700-7. doi: 10.1161/01.cir.0000012750.08480.55.
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.
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.
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.
α1 - 肾上腺素能受体（α1 - ARs）在心血管稳态中起关键作用。然而，α1 - AR亚型在体内的功能作用仍不清楚。本研究的目的是评估α1b - AR对心血管系统的影响。
在缺乏α1 - AR的转基因小鼠（KO）及其野生型对照（WT）中，我们评估了通过渗透泵持续给药（18天）去甲肾上腺素、血管紧张素II和亚升压剂量的去氧肾上腺素所诱导的血压变化情况以及心血管重塑。我们的结果表明，去甲肾上腺素仅使WT小鼠的血压水平升高。相比之下，血管紧张素II诱导的高血压状态在WT和KO小鼠中相当。去氧肾上腺素在WT或KO小鼠中均未改变血压水平。仅在WT小鼠中观察到去甲肾上腺素引起的心脏肥大和富营养化血管重塑，并且这种效应与高血压状态无关，因为它与亚升压剂量去氧肾上腺素输注期间观察到的效应相似。最后，胸主动脉缩窄诱导的心脏肥大在WT和KO小鼠中相当。
我们的数据表明，缺乏α1b - AR可预防去甲肾上腺素引起的动脉血压慢性升高，并同时独立于血压水平预防肾上腺素能激活引起的心血管重塑。
