Abstract / Summary
Abstract This study investigated the differential regulation of atrial and brain natriuretic peptides (ANP and BNP, respectively) and their renal receptors (NPR-A and NPR-C) in two experimental models of hypertension - DOCA-Salt (DS) and Renovascular (RV) - and their association with target organ damage. Male Sprague-Dawley rats were assigned to Control, DS, or RV groups and evaluated at 2, 6, and 12 weeks for systolic blood pressure (SBP), plasma ANP and BNP levels, renal gene and protein expression of NPR-A and NPR-C, and tissue markers of inflammation and fibrosis. Despite comparable increases in SBP, plasma ANP levels rose markedly in DS, while BNP increased only in RV. Renal NPR-A and NPR-C expression showed time-dependent upregulation in DS, but decreased at mid-stage in RV, returning to baseline at 12 weeks. Both hypertensive models exhibited increased expression of proinflammatory (TNF-α, IL-6, NF-κB) and profibrotic (TGF-β1) markers in the kidney and thoracic aorta, with DS showing earlier onset of molecular changes. These findings suggest that ANP is more responsive to possible volume overload, as suggested by sodium retention and atrial distension, although direct evidence of fluid expansion was not measured in this study, while BNP reflects pressure-driven stress. The earlier and more pronounced inflammatory and fibrotic responses observed in DS indicate that volume overload may accelerate target organ damage more than pressure overload. This highlights the distinct pathophysiological mechanisms underlying different hypertensive states and supports the relevance of natriuretic peptides as biomarkers and potential modulators of organ injury progression.