Altered cardiovascular reflexes responses in conscious Angiotensin-(1-7) receptor Mas-knockout mice

This study evaluated the physiological importance of Angiotensin-(1-7) receptor Mas on reflex control of circulation. Experiments were performed in male Mas-knockout (Mas-KO) and Wild Type (WT) conscious mice (12–20 wk of age). Baroreceptor reflex was evaluated by the bradycardic response induced by phenylephrine (0.25 μg/5 μl, i.v.). Bezold–Jarisch reflex was evaluated by phenylbiguanide (0.5 μg/5 μl, i.v.) and chemoreflex by potassium cyanide (2.5 μg/5 μl, i.v.). Baseline mean arterial pressure was higher in Mas-KO (n = 14) as compared with WT mice (n = 18) (118 ± 1 mm Hg vs. 109 ± 2 mm Hg); however, heart rate was similar in both strains (615 ± 30 bpm vs. 648 ± 13 bpm). Baroreflex bradycardia was lower (0.78 ± 0.44 ms/mm Hg vs. 1.30 ± 0.14 ms/mm Hg) in Mas-KO compared with WT mice. The depressor (−17 ± 5 mm Hg vs. −45 ± 6 mm Hg) and bradycardic (−212 ± 36 bpm vs. −391 ± 29 bpm) components of the Bezold–Jarisch reflex were also lower in Mas-KO mice. In addition, chemoreflex pressor response (+20 ± 3 mm Hg vs. +12 ± 0.8 mm Hg) and bradycardic response (−250 ± 74 bpm vs. −52 ± 26 bpm) were significantly higher in Mas-KO. These results further advances previous studies by showing that the lack of Mas receptor induced important imbalance in the neural control of blood pressure, altering not only the baroreflex but also the chemo- and Bezold–Jarisch reflexes.

Research highlights▶ Genetic deletion of the Ang-(1-7) receptor Mas impaired the baroreflex bradycardia. ▶ Cardiovascular responses of Bezold–Jarisch reflex were lower in Mas-knockout mice. ▶ Mas-deficiency in mice increased the pressor and bradycardic chemoreflex responses. ▶ Actions of Ang-(1-7) on cardiovascular reflexes seem to oppose those mediated by Ang II.