Abstract
The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats by pressure (renovascular) or volume overload (DOCA-salt) during 6 and 12 weeks of treatment. We also studied the consecutive combination of both models in inverse sequences: RV 6 weeks/DS 6 weeks and DS 6 weeks/RV 6 weeks. All treated groups developed hypertension. Cardiac hypertrophy and left ventricular ANP gene expression were more pronounced in single DS than in single RV groups. BNP gene expression was positively correlated with left ventricular hypertrophy only in RV groups, while ANP gene expression was positively correlated with left ventricular hypertrophy only in DS groups. Combined models exhibited intermediate values between those of single groups at 6 and 12 weeks. The latter stimulus associated to the second applied overload is less effective than the former to trigger cardiac hypertrophy and to increase ANP and BNP gene expression. In addition, we suggest a correlation of ANP synthesis with volume overload and of BNP synthesis with pressure overload-induced hypertrophy after a prolonged treatment. Volume and pressure overload may be two mechanisms, among others, involved in the differential regulation of ANP and BNP gene expression in hypertrophied left ventricles. Plasma ANP levels reflect a response to plasma volume increase and volume overload, while circulating BNP levels seem to be regulated by cardiac BNP synthesis and ventricular hypertrophy.
Highlights
Hemodynamic overload is a major determinant of the cardiac morphometric and functional response in cardiovascular diseases
We aimed to identify differential profiles of Systolic Blood Pressure and Cardiac Hypertrophy
The development of hypertension in response to renovascular hypertension (RV) was gradual and time-dependent, in agreement with previous studies in this model (Gao et al, 2005) while in DOCA-salt hypertension (DS) the blood pressure reached a plateau at 6 weeks, with higher levels than RV, and persisted elevated with no further increase up to 12 weeks
Summary
Hemodynamic overload is a major determinant of the cardiac morphometric and functional response in cardiovascular diseases. The natriuretic peptide (NP) family includes atrial (ANP) and B-type (BNP) natriuretic peptides that are secreted by the heart and are important regulators of cardiovascular homeostasis. They act on target organs through guanylyl cyclase- coupled receptors to induce diuresis, natriuresis and vasodilation, reducing cardiac preload and afterload in response to stress. Elevated circulating levels are related to increased atrial wall stretch and ventricular synthesis due to left ventricular hypertrophy (Goetze et al, 2020); the response of ANP and BNP throughout transitions between pressure and volume overload is not well characterized
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