OS 29-05 RENAL DENERVATION ATTENUATES ALDOSTERONE EXPRESSION AND ASSOCIATED CARDIOVASCULAR PATHOPHYSIOLOGY IN ANGIOTENSIN II-INDUCED HYPERTENSION

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Abstract

Objective:

The sympathetic nervous system interacts with the renin-angiotensin-aldosterone system (RAAS) contributing to cardiovascular diseases. In this study, we sought to determine if renal denervation (RDN) inhibits aldosterone expression and associated cardiovascular pathophysiological changes in angiotensin II (Ang II)-induced hypertension.

Design and Method:

Bilateral RDN or SHAM operation was performed before chronic 14-day Ang II infusion (200 ng/kg/min) in male Sprague-Dawley rats. Blood pressure was measured by telemetry and tail-cuff method. Cardiovascular hypertrophy was evaluated by histopathology and transthoracic echocardiography.

Results:

Bilateral RDN blunted Ang II-induced hypertension and ameliorated the mesenteric vascular dysfunction. Cardiovascular hypertrophy in response to Ang II was significantly attenuated by RDN. Moreover, Ang II-induced vascular and myocardial inflammation and fibrosis were suppressed by RDN with concurrent decrease in fibronectin and collagen deposition, macrophage infiltration, and MCP-1 expression. Interestingly, RDN also inhibited Ang II-induced aldosterone expression in the plasma, kidney and heart. This was associated with the reduction of calcitonin gene-related peptide (CGRP) in the adrenal gland. Ang II promoted aldosterone secretion which was partly attenuated by CGRP in the adrenocortical cell line, suggesting a protective role of CGRP in this model. Activation of transforming growth factor-β (TGF-β)/Smad and mitogen-activated protein kinases (MAPKs) signaling pathway was both inhibited by RDN especially in the heart.

Conclusions:

These results suggest that the renal sympathetic nerve regulation of Ang II-induced hypertension and associated cardiovascular pathophysiological changes is likely mediated by aldosterone with CGRP involvement.

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