Document Type
Article
Publication Date
11-17-2004
Publication Title
Physiological Genomics
ISSN
1094-8341
Volume
19
Issue/No.
3
First Page
255
Last Page
61
Abstract
The role of the angiotensin II type 2 receptor (AT2R) in cardiovascular physiology remains elusive. We have developed an in vivo lentiviral vector-mediated gene transfer system to study the physiological functions of the AT2R. Our objectives in this study were to determine whether the AT2R influences cardiac hypertrophy and myocardial and perivascular fibrosis in a nongenetic rat model of hypertension. Lentiviral vector containing the AT2R or saline was injected intracardially in 5-day-old Sprague-Dawley rats. This resulted in a persistent overexpression of the AT2R in cardiac tissues. At 15 wk of age, animals were infused with either 200 ng x kg(-1) x min(-1) of angiotensin II or saline by implantation of a 4-wk osmotic minipump. This resulted in an increase in blood pressure (BP) that reached maximal by 2 wk of treatment and was associated with a 123% increase in left ventricular wall thickness (LVWT) and a 129% increase in heart weight to body weight ratios (HW/BW). In addition, the increase in cardiac hypertrophy was associated with a 300% and 158% increase in myocardial and perivascular fibrosis, respectively. Cardiac transduction of the AT2R resulted in an 85% attenuation of LVWT, 91% attenuation of HW/BW, and a 43% decrease in myocardial fibrosis induced by angiotensin infusion. These improvements in cardiac pathology were observed in the absence of attenuation of high BP. Thus our observations indicate that long-term expression of the AT2R in the heart attenuates cardiac hypertrophy and fibrosis in a nongenetic rat model of hypertension.
NSUWorks Citation
Falcón, Beverly L.; Stewart, Jillian M.; Bourassa, Erick; Katovich, Michael J.; Walter, Glenn; Speth, Robert C.; Sumners, Colin; and Raizada, Mohan K., "Angiotensin II type 2 receptor gene transfer elicits cardioprotective effects in an angiotensin II infusion rat model of hypertension" (2004). HPD Articles. 109.
https://nsuworks.nova.edu/hpd_facarticles/109
ORCID ID
0000-0002-6434-2199
DOI
10.1152/physiolgenomics.00170.2004
Copyright
Copyright © 2004 the American Physiological Society
