The recently identified endogenous peptide apelin and its specific apelin receptor (APJ) are currently being considered as potential regulators in vascular tissue. Previously, we reported apelin mediates phosphorylation of myosin light chain and elicits vasoconstriction in vascular smooth muscle. In this study, physiological roles of the apelin-APJ system were investigated on atherosclerosis. In APJ and apolipoprotein E double-knockout (APJ ؊/؊ ApoE ؊/؊ ) mice fed a high-cholesterol diet, atherosclerotic lesions were dramatically reduced when compared with APJ Apelin receptor (APJ) is a G-protein-coupled receptor with seven transmembrane domains, and its endogenous ligand, apelin has been recently identified.1,2 The structures of APJ and apelin are highly conserved among species, and both are highly expressed in the cardiovascular system. 3,4 In the vascular system, APJ and apelin are known to be expressed in endothelium and vascular smooth muscle cells (VSMCs). Histological studies in rat show that the VSMCs of the medial layer of the aorta and pulmonary artery display intense staining for APJ-like immunoreactivity. 4 The vascular actions of apelin-APJ system may be complex. Under physiological conditions, the apelin-APJ system shows transient hypotension. The baseline blood pressure of APJ and angiotensin-type 1 receptor doubleknockout mice was significantly elevated compared with that of angiotensin-type 1 receptor knockout mice, 5 although APJ knockout (APJ Ϫ/Ϫ ) mice did not show any significant changes in cardiovascular parameters. In spontaneously hypertensive rats, APJ and apelin expression in both heart and aorta were markedly depressed compared with Wistar-Kyoto rats. 6 In aortae from type 2 diabetic db/db mice, APJ and apelin expression were

The renin-angiotensin system in the kidney plays a critical role in the regulation of renal hemodynamics and sodium handling through the activation of vascular, glomerular and tubular angiotensin II type 1 (AT1) receptor-mediated signaling. We previously cloned a molecule that specifically bound to the AT1 receptor and modulated AT1 receptor signaling in vitro, which we named ATRAP (for AT1 receptor-associated protein). The purpose of this study is to analyze the renal distribution of ATRAP and to examine whether ATRAP is co-expressed with the AT1 receptor in the mouse kidney. We performed in situ hybridization, Western blot analysis, and immunohistochemistry to investigate the expression of ATRAP mRNA and protein in the mouse kidney. The results of Western blot analysis revealed the ATRAP protein to be abundantly expressed in the kidney. Employing in situ hybridization and immunohistochemistry, we found that both ATRAP mRNA and the protein were widely distributed along the renal tubules from Bowman's capsules to the inner medullary collecting ducts. ATRAP mRNA was also detected in the glomeruli, vasculature, and interstitial cells. In all tubular cells, the ATRAP protein colocalized with the AT1 receptor. Finally, we found that the dietary salt depletion significantly decreased the renal expression of ATRAP as well as AT1 receptor. These findings show ATRAP to be abundantly and broadly distributed in nephron segments where the AT1 receptor is expressed. Furthermore, this is the first report demonstrating a substantial colocalization of ATRAP and AT1 receptor in vivo.

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The effects of a mixture of the Salacia reticulata (Kotala himbutu) aqueous extract and cyclodextrin (SRCD) on the development of obesity were examined. We studied the effects of SRCD on the elevation of plasma triacylglycerol levels induced by oral administration of a high-fat (HF) liquid diet to male Sprague-Dawley rats. The plasma triacylglycerol concentration was significantly lower in the SRCD-treated rats than in the control rats 4 h after HF diet administration (P<0.05). In a study of female C57BL/6 mice that consumed a solid HF diet containing 0, 0.2 or 0.5% SRCD ad libitum for 8 wk, the increases in body weight and visceral fat mass were less in those fed the diet supplemented with 0.5% SRCD than in those fed the HF diet (P<0.05). In male Sprague-Dawley rats fed a solid HF diet with or without 0.2% SRCD and restricted in energy intake to that of rats fed a normal diet for 35 d, the increases in body weight and visceral fat mass were smaller in the SRCD-supplemented rats (P<0.05). In addition, the energy efficiency and the plasma leptin and adiponectin concentrations were lower in the mice and rats that were administered SRCD than in those fed the HF diet alone (P<0.05). The inhibitory effects of SRCD on HF diet-induced obesity may be attributable to the inhibition of carbohydrate and lipid absorption from the small intestine. Therefore, SRCD may suppress the accumulation of visceral fat and the glucose intolerance that accompany this type of obesity.