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Central Pressor Response by Olmesartan in the Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats

DOI: 10.4137/CMRC.S5177

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Abstract:

Objectives: The major aims of the present study were to evaluate the effect of chronic oral treatment with olmesartan on cardiovascular response to exogenous angiotensin II (Ang II), and its relationship with the AT1 receptor (AT1R) mRNA in rostral ventrolateral medulla (RVLM) of spontaneously hypertensive rats (SHR). Methods: SHR (12 weeks old) were treated with olmesartan, 30 mg/(kg . day), in drinking water. 4 weeks later, Ang II (100 pmol) was microinjected into the RVLM, and arterial pressure and the heart rate were observed. Results: The blood pressure of all SHR-olme rats reach near normal level during breeding period. Ang IIresulted in an increase in mean arterial pressure (MAP) of each group. While, the increase of MAP in olmesartan-treated SHR was significantly smaller than that in untreated SHR(26.3 ± 0.75 mmHg vs. 47.2 ± 1.41 mmHg, n = 10, P < 0.01 ); however, it was still greater than that in WKY rats(26.3 ± 0.75 mmHg vs. 21.5 ± 0.72 mmHg, n = 10, P < 0.05). The heart rate (HR) of the each group was also increased, but there was no statistical significance among groups. In addition, AT1R mRNA in RVLM was measured by RT-PCR and analyzed with optic density. It demonstrated that the mean optic density (MOD) of AT1R mRNA in olmesartan-treated SHR was significantly reduced compared with untreated SHR(0.94 ± 0.41 vs. 2.41 ± 0.37, n = 10, P < 0.01); however, it was still higher than that in WKY rats(0.94 ± 0.41 vs. 0.81 ± 0.22, n = 10, P < 0.05). Conclusions: These results demonstrated that chronic oral treatment with olmesartan could obviously attenuate the exaggerated pressor response to exogenous Ang II and inhibit the excessive expression of AT1R in RVLM of SHR, so we presume olmesartan may attenuate central pressor response by reducing AT1R in RVLM of SHR.

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