T L Broderick1, Y Wang, J Gutkowska, D Wang, M Jankowski. 1. Laboratory of Diabetes and Exercise Metabolism, Departmentof Physiology, MidwesternUniversity, AZ 85308, USA. tbrode@midwestern.edu
Abstract
AIM: pulmonary hypertension (PH) in the rat leads to right ventricular (RV) hypertrophy, inflammation and increased natriuretic peptide (NP) levels in plasma and RV. Because the release of nitric oxide (NO) and atrial natriuretic peptide (ANP) is a function of the oxytocin receptor (OTR), we examined the effect of PH on gene and protein expression of OTR, NP (A, atrial; B, brain) and receptors (NPRs), nitric oxide synthases (NOS), interleukin (IL)-1β, IL-6 and tumour necrosis factor-α in the hypertrophied RV in a model of PH. METHODS: RV hypertrophy was induced in male Sprague-Dawley rats with monocrotaline (MCT; 60 mg kg(-1) ) and was confirmed by the presence of an increased RV weight and RV-to-[left ventricle (LV) and septum] ratio. RESULTS: in the RV of MCT-treated rats, a approximately 40% reduction in OTR mRNA and protein was observed compared with the RV of control rats. This reduction was associated with increased transcripts of ANP and BNP in both ventricles and a corresponding increase in NP receptor mRNA expression for receptors A, B and C. Protein expression of inducible NOS was increased in the RV, whereas endothelial NOS transcripts were increased only in the LV of MCT-treated rats. In the RV of MCT-treated rats, downregulation of OTR was also associated with increased mRNA expression of IL-1β and IL-6. CONCLUSION: our results show that downregulation of the OTR in the RV of MCT-treated rats is associated with increased expression of NP and their receptors as well as IL-1β and IL-6. This reduction in OTR in RV myocardium may have an impact on cardiac function in the MCT-induced model of PH.
AIM: pulmonary hypertension (PH) in the rat leads to right ventricular (RV) hypertrophy, inflammation and increased natriuretic peptide (NP) levels in plasma and RV. Because the release of nitric oxide (NO) and atrial natriuretic peptide (ANP) is a function of the oxytocin receptor (OTR), we examined the effect of PH on gene and protein expression of OTR, NP (A, atrial; B, brain) and receptors (NPRs), nitric oxide synthases (NOS), interleukin (IL)-1β, IL-6 and tumour necrosis factor-α in the hypertrophied RV in a model of PH. METHODS: RV hypertrophy was induced in male Sprague-Dawley rats with monocrotaline (MCT; 60 mg kg(-1) ) and was confirmed by the presence of an increased RV weight and RV-to-[left ventricle (LV) and septum] ratio. RESULTS: in the RV of MCT-treated rats, a approximately 40% reduction in OTR mRNA and protein was observed compared with the RV of control rats. This reduction was associated with increased transcripts of ANP and BNP in both ventricles and a corresponding increase in NP receptor mRNA expression for receptors A, B and C. Protein expression of inducible NOS was increased in the RV, whereas endothelial NOS transcripts were increased only in the LV of MCT-treated rats. In the RV of MCT-treated rats, downregulation of OTR was also associated with increased mRNA expression of IL-1β and IL-6. CONCLUSION: our results show that downregulation of the OTR in the RV of MCT-treated rats is associated with increased expression of NP and their receptors as well as IL-1β and IL-6. This reduction in OTR in RV myocardium may have an impact on cardiac function in the MCT-induced model of PH.
Authors: Tamara Merz; Britta Lukaschewski; Daniela Wigger; Aileen Rupprecht; Martin Wepler; Michael Gröger; Clair Hartmann; Matthew Whiteman; Csaba Szabo; Rui Wang; Christiane Waller; Peter Radermacher; Oscar McCook Journal: Intensive Care Med Exp Date: 2018-10-19