Does AVP deficiency or V1a/V2 receptor blockade with conivaptan reduce cardiac fibrosis in a rat model of abdominal aortic stenosis?
In a rat model of hypertensive heart disease, AVP deficiency or V1a/V2 receptor blockade with conivaptan significantly reduced and reversed cardiac fibrosis while improving hemodynamic and structural outcomes.
Cardiac fibrosis represents a consequence of hypertensive heart disease and is associated with ventricular dysfunction, arrhythmias, and mortality. Arginine vasopressin (AVP) promotes myofibroblast proliferation and collagen synthesis through V1a receptors. While hepatic studies suggest that AVP deficiency attenuates fibrosis, its cardiac impact remains unclear. This study evaluated the effects of AVP deficiency induced by neurointermediate pituitary lobectomy (NIL) and pharmacological V1a/V2 blockade with conivaptan (CV) in rats with fibrosis from abdominal aortic stenosis (AAC). Wistar rats were divided into seven groups with 10 animals each. Clinical variables and histopathology (H&E, Masson's trichrome, picrosirius red) were assessed. ANOVA, Fisher and Mantel-Cox tests were applied. The Fibrosis (F) group developed hypertrophy, hypertension, higher arrhythmia risk and increased fibrosis. In contrast, F+NIL and F+CV showed blood pressure and cardiac morphology comparable to controls, reduced arrhythmia risk and significantly less fibrosis. Histologically, F+NIL achieved partial regression, whereas F+CV nearly normalized tissue architecture. In conclusion, AVP deficiency or receptor blockade decreases and reverses AAC-induced fibrosis, improving hemodynamic, electrical, and structural outcomes. V1a/V2 blockade emerges as a potential therapeutic strategy.
Limón‐Mendoza et al. (Thu,) studied this question.