Blockade of central angiotensin II AT1 receptors attenuates acute intermittent hypoxia‐induced sympathetic long‐term facilitation (S‐LTF)

Abstract

After exposure to acute intermittent hypoxia (AIH) and while undergoing continuous normoxic ventilation, a progressive increase of sympathetic nerve discharge (SND) is observed in the anesthetized rat. This phenomenon, referred to as post‐AIH sympathetic long‐term facilitation (S‐LTF), involves neuroplasticity resulting, at least in part, from repetitive arterial chemoreceptor activation, but the underlying mechanisms remain to be determined. Evidence indicates that post‐AIH S‐LTF is largely unaffected by intravenous injection of the angiotensin II (AngII) AT1 receptor antagonist losartan. Because AIH repetitively increases renal SNA in associated with large amplitude reductions of arterial pressure and thus renal perfusion pressure, both of which potently stimulate the renin‐AngII system, we hypothesized that central AngII actions contribute to post‐AIH S‐LTF. Anesthetized male rats received an injection (2 μl) of losartan (40 pmol) or vehicle (aCSF) into a lateral cerebral ventricle 20 minutes before exposure to a 1 hour AIH protocol, which consisted of 10 cycles of changing FiO2 from 100% to 15% every 3 minutes. Losartan significantly attenuated (p<0.001) the increase of splanchnic SND caused by AIH (vehicle: 112±34%, n=4 vs losartan: 27±7%, n=7). These data indicate that AngII acting at central AT1 receptors contributes to post‐AIH S‐LTF. When considered together with literature evidence, we conclude that the AngII signal of AIH is generated centrally, not peripherally.Support or Funding InformationNIH HL088052 & AHA 25710176 (GMT)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.