Angiotensin type 2 receptors (AT2R) over expression in the nucleus of the solitary tract (NTS) attenuate renovascular hypertension

Abstract

We have demonstrated that AT2R overexpression in the NTS decreases mean arterial pressure (MAP) in normotensive rats. The aim of the present study was to investigate the effects of AT2R overexpression in the NTS in two kidney 1 clip (2K1C) hypertensive rats. Holtzman male rats (150–180 g, n = 5–6/group) were implanted with telemetry transducers into the abdominal aorta followed by a silver clip implant in the left renal artery. Three weeks after the 2K1C surgery the NTS was microinjected (200 nl/site, 5 sites) with either adeno‐associated virus vector AAV2‐CBA‐AT2R (1×108 gc) or AAV2‐CBA‐eGFP (1×109 gc) for the over expression of AT2R or GFP, respectively. At that time period, rats were hypertensive (134±3 mmHg light period and 133±4 mmHg dark period) compared to baseline levels (light period: 101±3 mmHg; dark period: 110±5 mmHg). Three to 4 weeks after the NTS injections (6–7 weeks after 2K1C), at which time AT2R or GFP expression has reached maximal (and stable) levels, MAP reached values of 171±10 mmHg light period and 190±8 mmHg dark period in GFP rats. In the AT2R transduced 2K1C rats, the increase in MAP was significantly lower compared to GFP animals (151±6 mmHg light period; 153±7 mmHg dark period: p<0.05 vs. GFP group). These results suggest that overexpression of AT2R in the NTS impairs the development of renovascular hypertension.Supported by: PNPD/CAPES, CNPq and NIH Grant HL 076803