Abstract
We recently showed the presence of ACE2 in brain regions involved in cardiovascular (CV) regulation. Although angiotensin (Ang)(1-7) is known to increase cardiac baroreflex sensitivity (CBS), the role of ACE2 is unclear. Therefore, we investigated ACE2 role in modulating CBS in ACE2 KO (n=5), exhibiting a high blood pressure (BP) phenotype, and control littermates (n=4). Anesthetized mice were implanted with carotid and jugular catheters for BP and heart rate monitoring and drug infusion, respectively. CBS (bpm/mmHg) was determined following random infusion of phenylephrine (50 ng/min iv) and sodium nitroprusside (5 μg/min iv). In ACE2 KO mice, CBS is significantly altered (−2.8±0.3) compared to control mice (−4.4±0.3; P<0.05) suggesting higher brain Ang-II levels in this model. To confirm the participation of central Ang-II, the experiment was repeated following central blockade of AT1 receptors with Losartan (10 μg/200 nl icv). Although Losartan had no effect on baseline BP in control mice (+1±1 mmHg; P>0.05), it significantly decreased BP in ACE2 KO mice (−11±2 mmHg; P<0.05). Moreover, AT1 receptor blockade partially restored CBS in ACE2 KO mice (−3.3±0.3; P<0.05). These data show that ACE2 is tonically involved in the maintenance of baseline BP and in the central regulation of CV function, offering a new target for the treatment of hypertension and other CV diseases. Support: NIH NS052479 and P20 RR018766
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