Activation of TRPV1 by Dietary Capsaicin Improves Endothelium-Dependent Vasorelaxation and Prevents Hypertension. * Highlights * Dietary capsaicin consumption reduces blood pressure * Capsaicin stimulates Ca2+ influx via TRPV1 in endothelium * Capsaicin increases PKA phosphorylation and NO production in a Ca2+-dependent manner * Vascular benefit is related to capsaicin activation of endothelial TRPV1. Summary: Some plant-based diets lower the cardiometabolic risks and prevalence of hypertension. New evidence implies a role for the transient receptor potential vanilloid 1 (TRPV1) cation channel in the pathogenesis of cardiometabolic diseases. Little is known about impact of chronic TRPV1 activation on the regulation of vascular function and blood pressure. Here we report that chronic TRPV1 activation by dietary capsaicin increases the phosphorylation of protein kinase A (PKA) and eNOS and thus production of nitric oxide (NO) in endothelial cells, which is calcium dependent. TRPV1 activation by capsaicin enhances endothelium-dependent relaxation in wild-type mice, an effect absent in TRPV1-deficient mice. Long-term stimulation of TRPV1 can activate PKA, which contributes to increased eNOS phosphorylation, improves vasorelaxation, and lowers blood pressure in
genetically hypertensive rats. We conclude that TRPV1 activation by dietary capsaicin improves endothelial function. TRPV1-mediated increase in NO production may represent a promising target for therapeutic intervention of hypertension.Hypertension is a major risk factor for the increased incidence of stroke, coronary heart disease, and renal insufficiency (Ong et al., 2007). Lowering high blood pressure reduces the risks to develop cardiovascular events (Cushman, 2001). Epidemiological studies show that multiple dietary factors affect blood pressure. Over the past decade, reducing sodium intake, increasing potassium intake, and consuming fruits and vegetables based on the DASH diet have emerged as effective antihypertensive strategies (Appel et al., 1997,Lichtenstein et al., 2006). Capsium species, or hot peppers, are consumed worldwide as vegetables and spices. Capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide) is the major pungent ingredient in hot pepper and gives a flavor to food without increasing calories. Capsaicin increases thermogenesis by enhancing catecholamine secretion from adrenal medulla, decreases weight gain, and adipogenesis by enhancing energy metabolism (Hachiya et al.,
2007,Kawabata et al., 2006,Ohnuki et al., 2001,Zhang et al., 2007). Capsaicin is a highly selective agonist for the transient receptor potential vanilloid 1 (TRPV1) cation channel (Caterina et al., 1997). TRPV1, a polymodal nonselective cation channel, is expressed in sensory neurons and also present in nonneuronal tissues including blood vessels (Nilius, 2007,Pedersen et al., 2005,Vennekens et al., 2008). Apart from its role as a potent analgesic (Caterina et al., 2000), capsaicin exerts effects in the cardiovascular system (Gupta et al., 2007,Pacher et al., 2004). However, the effects of capsaicin on vascular tone and arterial pressure are a paradox. Acute or short-term administration of capsaicin has mixed effects, either increasing or lowering arterial pressure transiently in human and rodents (del Carmen Garcia et al., 2003,Hachiya et al., 2007,Li and Wang, 2003). Capsaicin produces relaxation in several arterial in vitro preparations, which may be mediated by the releases of calcitonin gene-related peptide (CGRP) and substance P from perivascular sensory nerve terminals (Holzer, 1992,Li and Wang, 2003,Rubino and Burnstock, 1996). Alternatively, capsaicin is reported to increase the nitric oxide (NO) metabolites production by human vein endothelial cells (ECs) (Lo et al., 2003). Although TRPV1 is proposed to be involved in Dahl salt-sensitive hypertension (Wang and Wang, 2006), its
exact mechanism is poorly understood. Little is known about the impact of chronic activation of TRPV1 on the regulation of vascular function and blood pressure. We hypothesized that dietary capsaicin chronically activates TRPV1, which contributes to the vascular benefits. We provide in vivo and in vitro experimental evidence demonstrating that long-term activation of TRPV1 can actually increase the phosphorylated levels of protein kinase A (PKA) and endothelial NO synthase (eNOS) in mesenteric arteries and plasma levels of NO metabolites, augment endothelium-dependent relaxation, and lower arterial pressure in hypertensive rats. Our results suggest that endothelial TRPV1 is a potential therapeutic target in the management of hypertension and related vascular diseases. Authors: Dachun Yang, Zhidan Luo, Shuangtao Ma, Wing Tak Wong, Liqun Ma, Jian Zhong, Hongbo He, Zhigang Zhao, Tingbing Cao, Zhencheng Yan, Daoyan Liusend email, William J. Arendshorst, Yu Huang, Martin Tepel, Zhiming Zhu – Third Military Medical University (TMMU), located in Chongqing municipality, is a national key university with long history. The university covers an area of about 205.63 hectares, with a built-up area of 155.13 hectares. The university has a library with a collection
of books amounting to 620,000, and owns equipments and devices with a total value of 1.832 billion RMB Yuan.For many years, the university is renowned for its quality education and ranks among the leading group of medical universities in China. The university has established 14 specialties including clinical medicine, preventive medicine, laboratory medicine, medical imageology, pathologic diagnosis, nuclear medicine, altitude medicine, biomedical engineering, experimental medicine, nursing, pharmacy, nutrition and food hygiene, biotechnology and computer utility. There are 59 subjects that are approved to confer doctor’s degrees while 71 to confer master’s degrees.The university has more than 700 professors and associate professors, among whom 2 are academicians of Chinese Academy of Engineering and 195 are enjoying governmental allowance from the State Council. university holds 17 National Key Subjects, 1 National Key Laboratory and 5 Post-doctoral Research Centers of senior subjects. Till now, it has obtained more than 1500 S & T achievements marked by 6 National Awards for Scientific and Technological Progress (First Prize). There are 3 general teaching hospitals attached to TMMU and all of them are with good reputations in China. With a great capacity of 5000 beds in total, the 3
affiliated hospitals have a batch of world famous specialized departments like burns, respiratory diseases, hepatobiliary surgery, and chest surgery. The treatment of burns and hepatobiliary duct calculus are in the world leading position. For years, a number of new clinical skills and methods have been developed and some treatments were firstly carried out by these hospitals domestically. This includes pediatric heart transplant, heart-kidney transplant, successful separation of conjoined twins and ultrasound-mediated disruption for coronary artery diseases. In addition, the operational skills of liver allograft, pancreas-kidney transplant, and kidney transplant are at advanced level in the country, and the clinical application of high-tech means like artificial organs, molecular and gene therapies has also achieved a great breakthrough.The university always supports international academic exchanges and cooperation in a wide range and has established bilateral relations with more than 50 universities from 16 countries or regions. In recent five years, more than 1000 teachers were sent abroad to lecture, investigate and to pursue a further training. sources: cell.com & tmmu.com.cn
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