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      Maitake Mushroom Extracts Ameliorate Progressive Hypertension and Other Chronic Metabolic Perturbations in Aging Female Rats

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          Abstract

          Objective: We assessed the ability of two commercially-available fractions labeled SX and D derived from the edible maitake mushroom to overcome many age-associated metabolic perturbations such as progressive, age-related elevation of blood pressure, over activity of the renin-angiotensin system (RAS), decreased insulin sensitivity, and inflammation in an in vivo laboratory model.

          Design and Method: We divided forty mature, female Sprague-Dawley rats (SD) into five groups of eight. SD ingested regular rat chow containing added sucrose (20% w/w). The groups received baseline diet alone (control) or baseline diet containing captopril, niacin-bound chromium, maitake fraction SX, or maitake fraction D. In addition to blood pressure readings, the following procedures were implemented: losartan and insulin challenges, evaluation of serum ACE activity, glucose tolerance testing, blood chemistries, LNAME challenge, and measurement of various circulating cytokines.

          Results: We found that implementation of all test conditions stopped the gradual elevation of systolic blood pressure (SBP) in the SD over the four months of study, even reversing some of the previous elevation that occurred over time. In general, the treatment groups showed decreased activity of the RAS estimated by less lowering of SBP after losartan challenge and decreased serum ACE activity and were more sensitive to exogenous insulin challenge. TNFa levels decreased in all four test groups suggesting a lessening of the inflammatory state.

          Conclusions: We believe our data suggest that maitake mushroom fractions lessen age-related hypertension, at least in part, via effects on the RAS; enhance insulin sensitivity; and reduce some aspects of inflammation -- actions that should lead to a longer, healthier life span.

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          Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure.

          Consumption of pomegranate juice which is rich in tannins, possess anti-atherosclerotic properties which could be related to its potent anti-oxidative characteristics. As some antioxidants were recently shown to reduce blood pressure, we studied the effect of pomegranate juice consumption (50 ml, 1.5mmol of total polyphenols per day, for 2 weeks) by hypertensive patients on their blood pressure and on serum angiotensin converting enzyme (ACE) activity. A 36% decrement in serum ACE activity and a 5% reduction in systolic blood pressure were noted. Similar dose-dependent inhibitory effect (31%) of pomegranate juice on serum ACE activity was observed also in vitro. As reduction in serum ACE activity, even with no decrement in blood pressure, was previously shown to attenuate atherosclerosis, pomegranate juice can offer a wide protection against cardiovascular diseases which could be related to its inhibitory effect on oxidative stress and on serum ACE activity.
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            Proinflammatory actions of angiotensins.

            Many experimental data have suggested that the renin-angiotensin system participates in immune and inflammatory responses. Angiotensin II is involved in several steps of the inflammatory process: mononuclear cells respond to angiotensin II stimulation (cell proliferation and chemotaxis); angiotensin II regulates the recruitment of proinflammatory cells into the site of injury (mediated by the expression of vascular permeability factors, adhesion molecules and chemokines by resident cells); inflammatory cells can produce angiotensin II, and might therefore contribute to the perpetuation of tissue damage. In this review, we summarize the proinflammatory properties of angiotensin II, to demonstrate the novel role of this vasoactive peptide as a true cytokine. We will show the information obtained as a result of the pharmacological blockade of the renin angiotensin system, which has demonstrated that this system is involved in immune and inflammatory diseases. In this aspect, we discuss the molecular mechanism of angiotensin II-induced tissue damage, as well as its contribution to the pathogenesis of several diseases, including atherosclerosis, hypertension and renal damage, showing that angiotensin II plays an active role in the inflammatory response of these diseases.
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              Role of the renin-angiotensin system in vascular diseases: expanding the field.

              The renin-angiotensin system (RAS) has emerged as one of the essential links in the pathophysiology of vascular disease. Angiotensin (Ang) II, the main peptide of the RAS, was considered as a vasoactive hormone, but in the past years, this view has been modified to a growth factor that regulates cell proliferation/apoptosis and fibrosis. Recently, this view has been enlarged with a novel concept: Ang II participates in the inflammatory response, acting as a proinflammatory mediator. In resident vascular cells, Ang II produces chemokines, cytokines, and adhesion molecules, which contribute to the migration of inflammatory cells into the tissue injury. Ang II is also a chemotactic and mitogenic factor for mononuclear cells. The molecular mechanisms of Ang II-induced vascular damage are mediated by the activation of transcription factors, redox signaling systems, and production of endogenous growth factors. In addition, other components of the RAS could also be involved in the pathogenesis of cardiovascular diseases. The Ang II degradation product Ang III shares some of its properties with Ang II, including chemotaxis and production of growth factors and chemokines. All these data clearly demonstrate that Ang II is a true cytokine, show the complexity of the RAS in pathological processes, and provide some mechanistic responses of the beneficial effects of the treatment with RAS blockers in cardiovascular diseases.
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                Author and article information

                Journal
                Int J Med Sci
                ijms
                International Journal of Medical Sciences
                Ivyspring International Publisher (Sydney )
                1449-1907
                2010
                7 June 2010
                : 7
                : 4
                : 169-180
                Affiliations
                1. Georgetown University Medical Center, Department of Physiology, Washington, D.C. 20057, USA
                2. University of Houston College of Pharmacy, Department of Pharmacological and Pharmaceutical Services, Houston, TX 77204, USA
                3. Michigan State University College of Human Medicine, East Lansing, MI 48824-136, USA
                Author notes
                ✉ Corresponding author: Harry G. Preuss M.D., M.A.C.N., C.N.S., Professor of Physiology, Medicine, & PathologyGeorgetown University Medical Center, Basic Science Building, Room 231 B, 4000 Reservoir Road, NW, Washington, D.C. 20057. Work Phone 202-687-1441; Work Fax 202-687-8788; E mail: preusshg@ 123456georgetown.edu

                Conflict of Interest: The authors have declared that no conflict of interest exists.

                Article
                ijmsv07p0169
                10.7150/ijms.7.169
                2887057
                20567593
                4323b6ab-1696-4914-980b-79a3463f67e8
                © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
                History
                : 17 March 2010
                : 4 June 2010
                Categories
                Research Paper

                Medicine
                age-related hypertension,sugar-induced hypertension,insulin sensitivity,inflammation,maitake mushroom,maitake

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