Effects of pulmonary artery denervation on the renin-angiotensin-aldosterone system in pulmonary and right ventricular tissues in dogs with normal pulmonary pressure

Abstract

Objective To investigate the effects of pulmonary artery denervation(PADN)on pulmonary artery function outside of the nervous system. Methods Thirty-six beagles of 8-10 months old weighting 8-15 kg were randomized into six groups: a blank control group, an immediate post-surgery group, a 1 month post-surgery group, a 2 months post-surgery group, a 3 month post-surgery group, and a pulmonary artery hypertension(PAH)group, with six dogs in each group.Dogs in the blank control group received no treatment, and dogs in the surgery groups were treated with PADN and were then killed immediately after surgery, at 1, 2 or 3 months after surgery.PAH dogs were induced by dehydromonocrotaline, and they were killed at 8 weeks after treatment.Protein levels of angiotensin Ⅱ(Ang Ⅱ), angiotensin converting enzyme(ACE), angiotensin converting enzyme 2(ACE2), mineralocorticoid receptors(MR)and antibodies against aldosterone in dog pulmonary and right ventricular tissues were detected by Western blot.The mRNA expression of the Ang Ⅱ type 1 receptor(AT1R)was determined by real-time reverse transcription quantitative polymerase chain reaction(RT-qPCR). The protein expression ratio of ACE2 to ACE in lung and right ventricular tissues were calculated.Changes of the renin-angiotensin-aldosterone system(RAAS)in lung and right ventricular tissues were compared between the groups. Results In pulmonary tissues, protein levels of Ang Ⅱ, ACE2, MR, and AT-1R increased immediately after PADN(P=0.03, 0.03, 0.01 and<0.01), and the protein expression of ACE decreased(P<0.001), indicating that RAAS was activated immediately after PADN.Three months after PADN, AngⅡ protein levels declined significantly in lung tissues(P=0.030), and ACE2, ACE, MR, and AT-1 receptor protein expression had no obvious difference(P=0.670, 0.570, 0.180 and 0.349), compared with the blank control group.In right ventricular tissues, the protein expression of ACE2 was higher in the surgery groups than in the blank control group(P=0.0161), and there was no significant difference in the protein expression of Ang Ⅱ, ACE, MR, and AT-1 receptors(P=0.641, 0.134, 0.227 and 0.330). Conclusions RAAS activates immediately in dogs with normal pulmonary pressure after PADN, the damaging factors in pulmonary tissues are reduced and the vascular protective factors in right ventricular tissues are elevated at 3 months after PADN. Key words: Sympathectomg, chemical; Hypertension, pulmonary; Renin-angiotensin system