Renovascular hypertensive (2K1C) rats exhibit impaired baroreflexes. Here we studied the effects of increased angiotensin type 2 receptor (AT2R) expression in the nucleus of the solitary tract (NTS) on baroreflex function of 2K1C rats and on selected gene levels at this site. Male Holtzman rats (150-180g) were anaesthetized with a mixture of ketamine (80 mg kg-1) and xylazine (7 mg kg-1, both i.p.) and the left renal artery was partially obstructed with a silver clip (0.2 mm width) or sham surgery. Three weeks later, 2K1C and sham rats were anaesthetized as above and microinjected in the NTS with either AAV2-CBA-AT2R (1.2 x 1012 genomic copies (gc)/ml; n = 6-8/group) or AAV2-CBA-eGFP (1.8 x 1012 gc/ml; n = 4-6/group) to elicit chronic increases in AT2R or GFP (control) expression respectively. Thirty days later, 2K1C and sham rats were anaesthetized as above and femoral artery and vein were cannulated to measure mean arterial pressure (MAP) and heart rate (HR) and perform drug infusions, respectively. The next day, phenylephrine (5 µg/kg, iv) and sodium nitroprusside (30 µg/kg, iv) were used to elicit respective pressor and depressor responses in conscious rats. Reflex HR responses were analyzed to each 10 mmHg change in MAP. Values are means ± S.E.M., compared by ANOVA. Baseline MAP in 2K1C-AT2R rats (173 ± 7 mmHg) was lower than in 2K1C-GFP rats (199 ± 9 mmHg; p <0.05). 2K1C-GFP rats exhibited a significant impairment of the baroreflex (slope: -0.95 ± 0.05, vs. sham-GFP -1.37 ± 0.06, p<0.05), which was improved in the 2K1C-AT2R rats (slope: -1.44 ± 0.07). Baroreflex in 2K1C-AT2R was similar to sham-AT2R rats (slope: -1.56 ± 0.06) or sham-GFP. Real time RT-PCR revealed that the lower angiotensin converting enzyme 2 (ACE 2) mRNA levels in 2K1C-GFP rats were normalized in the 2K1C-AT2R rats (sham-GFP: 0.23 ± 0.03; sham-AT2R: 0.18 ± 0.03; 2K1C-GFP: 0.03 ± 0.01; 2K1C-AT2R: 0.31 ± 0.07, p<0.05). The results suggest that increased AT2R expression in the NTS of 2K1C rats improves baroreflexes and increases ACE 2 levels and these factors may contribute to the reduction in blood pressure observed in these animals.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCC028
Poster Communications: Increased expression of angiotensin type 2 receptors in the nucleus of the solitary tract improves baroreflex function and angiotensin converting enzyme 2 levels in renovascular hypertensive rats
G. T. Blanch1, A. H. Freiria-Oliveira1, K. Rigatto2, H. Li3, E. Colombari1, C. Sumners4, D. S. Colombari1
1. Physiology and Pathology, School of Dentistry - Sao Paulo State University, Araraquara, Sao Paulo, Brazil. 2. Basic Science and Health, UFCSPA, Porto Alegre, Sao Paulo, Brazil. 3. Southern Medical University, Guangzhou, China. 4. Physiology and Functional Genomics, University of Florida, Gainsville, Florida, United States.
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Where applicable, experiments conform with Society ethical requirements.