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High-dose nitrate therapy recovers the expression of subtypes [alpha]1 and [beta]-adrenoceptors and Ang II receptors of the renal cortex in rats with myocardial infarction-induced heart failures
Ist Teil von
BMC cardiovascular disorders, 2020-02, Vol.20 (1)
Ort / Verlag
BioMed Central Ltd
Erscheinungsjahr
2020
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
Background Few studies examined the effect of long-acting nitrates on renal function in chronic heart failure (CHF). Thus, we aimed to investigate the effect of long-acting nitrate on the expression of adrenoceptors (AR) and angiotensin II receptor (ATR) subtypes of the renal cortex, in rats with myocardial infarction-induced CHF. Methods Rats were randomly divided into the following groups: control, sham-operated, CHF, low- and high-dose nitrate, positive drug control (olmesartan), and high-dose of long-acting nitrate + olmesartan. Ultrasound echocardiography markers were compared, and the levels of AR subtypes, AT.sub.1R, and AT.sub.2R were measured using reverse transcription-polymerase chain reaction and western blot analysis. Histopathology of the kidney was determined on hematoxylin and eosin-stained sections. Results CHF significantly increased plasma renin activity (PRA) and angiotensin II levels, upregulated AT.sub.1R expression and downregulated [alpha].sub.1A-, [beta].sub.1-, [beta].sub.2-AR, and AT.sub.2R expression compared to the sham control. High-dose nitrate or olmesartan alone, and especially in combination, decreased the levels of PRA and angiotensin II and downregulated the CHF-induced expression of AT.sub.1R, [alpha].sub.1A-, [beta].sub.1-, and [beta].sub.2-AR, and AT.sub.2R. CHF resulted in significant impairment of the renal tissue, including inflammatory cells infiltration to the tubular interstitium and surrounding the renal glomerulus, and tubular necrosis, which was alleviated in all treatment groups to different degrees. Conclusions Long-acting nitrates could reverse CHF-induced changes in AR and ATR subtypes in the kidney, and improve cardiac function to protect renal function. Compared with monotherapy, the combination of nitrates and olmesartan shows more significant benefits in regulating AR and ATR subtypes. Keywords: Chronic heart failure, Long-acting nitrate, Adrenoceptors, Ang II receptors, Renal function