In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 90, No. 5 ( 2002-03-22), p. 617-624
Abstract:
To examine the physiological importance of brain angiotensin II type 1 (AT 1 ) receptors, we developed a novel transgenic mouse model with rat AT 1a receptors targeted selectively to neurons of the central nervous system (CNS). A transgene consisting of 2.8 kb of the rat neuron-specific enolase (NSE) 5′ flanking region fused to a cDNA encoding the full open-reading frame of the rat AT 1a receptor was constructed and transgenic mice (NSE-AT 1a ) were generated. Two of six transgenic founder lines exhibited brain-selective expression of the transgene at either moderate or high levels. Immunohistochemistry revealed widespread distribution of AT 1 receptors in neurons throughout the CNS. This neuron-targeted overexpression of AT 1a receptors resulted in enhanced cardiovascular responsiveness to intracerebroventricular (ICV) angiotensin II (Ang II) injection but not to other central pressor agents, demonstrating functional overexpression of the transgene in NSE-AT 1a mice. Interestingly, baseline blood pressure (BP) was not elevated in either transgenic line. However, blockade of central AT 1 receptors with ICV losartan caused significant falls in basal BP in NSE-AT 1a mice but had no effect in nontransgenic controls. These results suggest that whereas there is an enhanced contribution of central AT 1 receptors to the maintenance of baseline BP in NSE-AT 1a mice, particularly effective baroreflex buffering prevents hypertension in this model. Used both independently, and in conjunction with mice harboring gene-targeted deletions of AT 1a receptors, this new model will permit quantitative and relevant investigations of the role of central AT 1a receptors in cardiovascular homeostasis in health and disease.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/01.RES.0000012460.85923.F0
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2002
detail.hit.zdb_id:
1467838-X
Bookmarklink
