Abstract P125: Visceral Adipose Tissue-derived Serine Protease Inhibitor Prevents the Development of Hypertension Through the Inhibition of Vascular Remodeling via Anti-Oxidative Mechanisms in Spontaneously Hypertensive Rats

Abstract

Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine originally identified in visceral adipose tissue of obese type 2 diabetic Otsuka Long-Evans Tokushima Fatty rats. We have been focusing on the direct vascular effects of vaspin and found that vaspin inhibits: 1) tumor necrosis factor-α-induced inflammatory responses in vascular smooth muscle cells (SMCs) via the anti-oxidative mechanisms, 2) platelet derived growth factor-BB-induced migration of SMCs, 3) apoptosis of vascular endothelial cells (ECs) mediated by methylglyoxal, a metabolite of glucose. Since vascular remodeling via inflammation and migration of vascular SMCs as well as apoptosis of ECs is an important process for the development of hypertension, it is suggested that vaspin has preventive roles on the pathogenesis of hypertension. However, it is not revealed whether vaspin affects the development of hypertension in in vivo hypertensive model. The aim of the present study was to explore it. Five-week-old male spontaneously hypertensive rats (SHR) were received an intraperitoneal injection of vaspin (1 μg/kg) or saline once daily for four weeks. Age-matched male Wistar-Kyoto (WKY) rats were used as a control. Blood pressure (BP) was measured using a tail-cuff method weekly. Isolated superior mesenteric arteries were used for the examination of vascular structural changes by a hematoxylin and eosin staining. Reactive oxygen species (ROS) generation was examined by an immunohistochemical staining to 4-hydroxy-2-nonenal (4-HNE), an end-product of lipid peroxidation by ROS. Vaspin significantly inhibited age-dependent elevation of BP in SHR (from 165.5 ± 3.9 mmHg to 153.1 ± 2.5 mmHg, n = 3, P < 0.05). Vaspin significantly inhibited vascular wall hypertrophy in SHR mesenteric artery (from 1.35±0.05 to 0.98±0.08-fold relative to WKY, n = 3, P < 0.05). Moreover, vaspin inhibited an increase of 4-HNE-positive area to vessel area ratio in SHR mesenteric artery (from 13.1±4.4 % to 4.6±0.4 %, n = 3). The present results demonstrate that vaspin inhibits the increase of BP through inhibiting vascular remodeling via anti-oxidative mechanisms in SHR.