ARGININE VASOPRESSIN DEFICIENCY INDUCES DECREASED CARDIAC FIBROSIS RATE AND MEAN ARTERIAL BLOOD PRESSURE IN RATS WITH EXPERIMENTAL ABDOMINAL AORTIC STENOSIS

Abstract

Cardiac fibrosis (CF) involves the accumulation of extracellular matrix proteins in the interstitial space, often seen in various cardiac pathologies. Each year, cardiovascular diseases claim the lives of 17.9 million people worldwide. Cardiac fibroblasts and myofibroblasts, equipped with vasopressin receptors (AVP), play a crucial role in regulating cell signaling pathways associated with CF development. AVP, an immunomodulatory hormone, influences immune responses, and its deficiency results in a decrease in immune activity. Abdominal aortic stenosis (AS) serves as an experimental model for left cardiac overload hypertension and CF. Neurointermediate pituitary lobectomy (NIL) induces a permanent decrease in circulating AVP levels, showcasing regression of hepatic fibrosis in liver damage models. The quest for effective alternative treatments for cardiac fibrosis poses a substantial challenge for researchers. In this experiment, groups of male Wistar rats weighing approximately 250 g (8/group) were categorized into: 1) Intact Control (IC), 2) Abdominal Aortic Stenosis (AS), 3) Neurointermediate pituitary lobectomy (NIL), and 4) AS+NIL. The AS and AS+NIL groups underwent abdominal aortic stenosis surgery on day one of the experiment. By week 5, the NIL and NIL+AS groups underwent NIL surgery. Prior to sacrifice at week 10, intracarotid mean blood pressure (MBP) was assessed in all groups. Following sacrifice, the hearts were removed, fixed in neutral formalin, and processed in paraffn for histopathological examination using H-E, Masson's trichrome, and Sirius red staining. Results revealed an elevated MBP in the AS group (156 ± 27.1 vs. 114 ± 30 mmHg in the IC), normalized in the AS+NIL group (110 ± 40.9 mmHg), and a mild decrease in the NIL group (87 ± 7.6 mmHg). The evaluation of CF in histological slides concurred with the MBP findings; a significant increase in CF occurred in the AS group compared to the IC, NIL, and AS+NIL groups, with almost complete reversion of CF observed in the AS+NIL group. In summary, this study demonstrates that AVP deficiency induces arterial hypotension, and in the AS+NIL group, AVP deficiency led to: 1) a decrease in blood pressure to normal levels and 2) reversion of cardiac fibrosis. Further experiments are warranted to determine if the decrease in blood pressure and cardiac overload are suffcient to inhibit profibrogenic mechanisms and/or activate antifibrogenic mechanisms. Additionally, investigations are needed to explore whether AVP deficiency, beyond inhibiting the inflammatory process, promotes the activation of antifibrogenic mechanisms. The present results offer new avenues for a deeper understanding of the molecular and cellular mechanisms through which AVP deficiency or the use of AVP receptor antagonists significantly influences fibrosis regulation in organ fibrotic diseases. Funding by Autonomous University of Aguascalientes (PIFF22-1). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.