Abstract-Hypertension and aging are associated with large artery structural remodeling and stiffening, which are known to increase cardiovascular risk. Relaxin is a peptide hormone with potent antifibrotic action in multiple organs. Although relaxin is able to reduce peripheral vascular resistance and improve arterial compliance in rats, it remains unclear whether the improvement in compliance is indirectly attributed to a vasodilatory action or whether relaxin is able to reverse arterial remodeling and stiffening directly in aged hypertensive animals. Senescent spontaneously hypertensive rats (17 months old) were treated with relaxin for 2 weeks (0.5 mg/kg per day) followed by a 1-week washout period.We determined large artery compliance using in vivo and in vitro techniques and quantified arterial remodeling by morphological and chemical means. Relaxin therapy significantly reversed aortic remodeling (ie, increases in vessel size, wall thickness, and collagen content) and improved arterial compliance, effects independent of its vasodilatory action. In relaxin-treated spontaneously hypertensive rats, arterial collagen content showed a greater reduction (Ϫ31%; PϽ0.05) than that of elastin (Ϫ8%) 4 Several studies have provided strong evidence for relaxin as a potent vasodilator in vitro and in vivo. [5][6][7] The signaling mechanisms involve stimulating nitric oxidase synthases or endothelin--mediated vasodilatory signaling 8 and antagonizing vasoconstriction induced by angiotensin II, endothelin 1, and catecholamines. 9 Conrad and colleagues 7,10 showed that treatment with relaxin either acutely or for a period of 10 days increased large artery compliance and cardiac output without a change in blood pressure in normotensive or hypertensive rats.Another unique feature of relaxin is its potent antifibrotic action. 11,12 In relaxin knockout mice, fibrosis occurs with aging in multiple organs. 11,[13][14][15] Conversely, administration of relaxin for 2 weeks effectively reversed organ fibrosis in relaxin knockout mice or other models of cardiac fibrosis, 11 including spontaneously hypertensive rats (SHR) showing reduced cardiac and renal fibrosis by relaxin therapy for 2 weeks. 16 Relaxin achieves its antifibrotic action through multiple mechanisms involving suppression of collagen synthesis via inhibiting fibroblast activation/proliferation and promotion of collagen degradation through activating matrix metalloproteinases. 11 Previous studies on the cardiovascular properties of relaxin have focused on its antifibrotic actions in the heart or blood pressure-lowering effect, 2,7 and it remains unknown whether chronic relaxin treatment in hypertensive models is able to reverse remodeling of large arteries. Progress in this area would advance our understanding of the therapeutic potential of relaxin. In the current study, we have addressed the hypothesis that relaxin therapy in SHRs is able to reverse large artery remodeling with accompanied improvement in arterial compliance. To make our findings more applicab...
Question Answering System [QAS] generates answer to various questions imposed by users. The QAS uses documents or knowledge base for extracting the answers to factoid questions and conceptual questions. Use of Frequently Asked Question (FAQ) base gives a satisfying results to QAS, but the limitation with FAQ base system is in the preparation of Question and Answer set as most of the questions are not predetermined.QAS using FAQ base fails if no semantically related questions are found in base, corresponding to the input question. This demands an automatic answering system as backup, which generates answer especially to conceptual questions.The work presented here gives a framework for automatic generation of answers to conceptual question especially "what", "why" and "how" type for frequently asked based, Question Answering System and in terms gradually builds up the FAQ base.
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