DISPARATE IMPACT OF PRIMARY HYPERTENSION ON RIGHT VERSUS LEFT HEART VENTRICLES OF MALES AND FEMALES WILD TYPE AND HAIRLESS STRAIN OF SPONTANEOUSLY HYPERTENSIVE RATS

Abstract

Objective: Poor adherence to lifestyle changes and antihypertensive drugs contributes to increase a risk for malignant cardiac arrhythmias. Hypertension contributes to myocardial structural remodeling, abnormalities in connexin43 (Cx43) which promote electrical instability and mechanical dysfunction. However, it is not known whether changes are confined solely to left heart ventricle (LV) or there is response of right heart ventricle (RV). SHR mimic human primary hypertension and hairless SHR is model of temperature acclimation characterized by increase thermogenesis. Aim of the study was to explore key factors involved in development of malignant arrhythmias and progression to heart failure, in left and right heart ventricles, of males and females wild type (WT) and hairless SHR. Design and method: 6-month-old males and females WT and hairless SHR and normotensive WKY strain of rats were housed at standard 22°C. Biometric parameters, including electro- and echo-cardiographic were registered. LV and RV tissue was used for immuno-labelling of Cx43 to detect its topology and western blotting for determination protein levels of Cx43, PKA, PKC∊, PKCδ and markers of extracellular matrix (ECM) remodelling: TGFβ, SMAD2/3, MMP-2 and collagen-1. Susceptibility of the heart to electrically-inducible VF was tested using isolated perfused heart technique. Results: Comparing to WKY, QT and QRS intervals were prolonged in WT SHR with normalisation in hairless SHR. Hypertension resulted in decrease in Cx43 with its abnormal topology in LV of males and less in hairless SHR but not in females. Cx43 levels and its topology were preserved in RV regardless rat strain and sex. There were no differences in protein levels of ECM-markers when comparing LV and RV in all strains. PKC∊ and PKCδ were increased in RV versus LV in both SHR strains. Hairless SHR males and females were less prone to inducible VF compared to WT SHR. Conclusions: Findings point out that hypertension-induced pro-arrhythmic disorders of Cx43 are related to the left while not to right heart ventricle in both hypertensive strains. There is a benefit of cold acclimation in hypertension that may contribute, to the protection from malignant cardiac arrhythmias and mechanical dysfunction. Supported by Vega2/0002/20,2/0006/23 and APVV21-0410.