Angiotensin-(1-7) antagonist, A-779, microinjection into the caudal ventrolateral medulla of renovascular hypertensive rats restores baroreflex bradycardia

Abstract: In the present study we evaluated the effect of caudal ventrolateral medulla (CVLM) microinjection of the main angiotensin (Ang) peptides, Ang II and Ang-(1-7), and their selective antagonists on baseline arterial pressure (AP) and on baroreceptor-mediated bradycardia in renovascular hypertensive rats (2K1C). Microinjection of Ang II and Ang-(1-7) into the CVLM of 2K1C rats produced similar decrease in AP as observed in Sham rats. In both Sham and 2K1C, the hypotensive effect of Ang II and Ang-(1-7) at the CVLM was blocked, for up to 30min, by previous CVLM microinjection of the Ang II AT1 receptor antagonist, Losartan, and Ang-(1-7) Mas antagonist, A-779, respectively. As expected, the baroreflex bradycardia was lower in 2K1C in comparison to Sham rats. CVLM microinjection of A-779 improved the sensitivity of baroreflex bradycardia in 2K1C hypertensive rats. In contrast, Losartan had no effect on the baroreflex bradycardia in either 2K1C or Sham rats. These results suggest that Ang-(1-7) at the CVLM may contribute to the low sensitivity of the baroreflex control of heart rate in renovascular hypertensive rats. [Copyright &y& Elsevier]