title: Pulmonary artery denervation improves pulmonary arterial hypertension induced right ventricular dysfunction by modulating the local renin-angiotensin-aldosterone system.
abstract: Pulmonary arterial hypertension (PAH) is commonly accompanied with the activation of the renin-angiotensin-aldosterone system (RAAS). Renal sympathetic denervation (RSD) reduces PAH partly through the inhibition of RAAS. Analogically, we hypothesized that pulmonary artery denervation (PADN) could reverse PAH and PAH-induced right ventricular (RV) dysfunction by downregulating the local RAAS activity.
  
  
  
  Twenty-five beagle dogs were randomized into two groups: control group (intra-atrial injection of N-dimethylacetamide, 3 mg/kg, n = 6) and test group (intra-atrial injection of dehydrogenized-monocrotaline, 3 mg/kg, n = 19). Eight weeks later, dogs in the test group with mean pulmonary arterial pressure (mPAP) ≥25 mmHg (n = 16) were reassigned into the sham (n = 8) and PADN groups (n = 8) by chance. After another 6 weeks, the hemodynamics, pulmonary tissue morphology and the local RAAS expression in lung and right heart tissue were measured.
  
  
  
  PADN reduced the mPAP (25.94 ± 3.67 mmHg vs 33.72 ± 5.76 mmHg, P < 0.05) and the percentage of medial wall thickness (%MWT) (31.0 ± 2.6 % vs 37.9 ± 2.8 %, P < 0.05) compared with the sham group. PADN attenuated RV dysfunction, marked with reduced atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and ratio of right ventricular to left ventricular plus septum weight [RV/(LV + S)]. Moreover, the local RAAS expression was activated in PAH dogs while inhibited after PADN.
  
  
  
  PADN improves hemodynamics and relieves RV dysfunction in dogs with PAH, which can be associated with the downregulating RAAS activity in local tissue.
authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, 68# Changle Road, Nanjing, 210006, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Division of Cardiology, Nanjing First Hospital, 68# Changle Road, Nanjing, 210006, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Jiang
authors.affiliation: Division of Cardiology, Nanjing First Hospital, 68# Changle Road, Nanjing, 210006, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, 68# Changle Road, Nanjing, 210006, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, 68# Changle Road, Nanjing, 210006, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Cardiology, Nanjing First Hospital, 68# Changle Road, Nanjing, 210006, China.
authors.forename: Du-Jiang
authors.initials: DJ
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, 68# Changle Road, Nanjing, 210006, China. huzuoying@aliyun.com.
authors.forename: Zuo-Ying
authors.initials: ZY
authors.lastname: Hu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004285:Dogs; D006439:Hemodynamics / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000150:complications / Q000378:metabolism / Q000601:surgery*; D011651:Pulmonary Artery / Q000294:innervation*; D012084:Renin-Angiotensin System / Q000502:physiology*; D013562:Sympathectomy / Q000379:methods*; D013564:Sympathetic Nervous System / Q000503:physiopathology / Q000601:surgery*; D018497:Ventricular Dysfunction, Right / Q000209:etiology / Q000503:physiopathology / Q000601:surgery*
keywords: Pulmonary arterial hypertension; Pulmonary artery denervation; Renin–angiotensin–aldosterone system; Right ventricular dysfunction