title: Reduced hemodynamic load aids low-dose resveratrol in reversing cardiovascular defects in hypertensive rats.
abstract: Cardiac hypertrophy and associated myocardial remodeling is one of the main complications of hypertension resulting in the development of heart failure. It is of great significance to explore novel treatments to reverse cardiac hypertrophy in hypertensives with or without affecting blood pressure. In the present study, we investigated whether low-dose resveratrol alone or in a combination with a blood pressure-lowering agent can reverse hypertension-induced cardiovascular dysfunction. Twenty-week-old male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats were treated with resveratrol (2.5 mg kg⁻¹ per day) and/or hydralazine (25 mg kg⁻¹ per day) for 8 weeks. Blood pressure, cardiac structure and function, and electrocardiogram measurements were examined. Pressure myography of resistance arteries, histological examinations of heart tissues, oxidative stress and inflammatory measurements were also preformed to assess the efficacy of the treatment. Although resveratrol treatment alone was ineffective in reducing systolic blood pressure, diastolic blood pressure, diastolic dysfunction and vascular remodeling, it significantly prevented the systolic impairment and reduced myocardial fibrosis, and reduced oxidative stress and inflammation in hypertensive rats. Furthermore, a combination of resveratrol with hydralazine treatment significantly reduced blood pressure, improved systolic and diastolic function, decreased fibrosis and improved vascular geometry. In summary, low-dose resveratrol itself was unable to reduce systolic blood pressure, diastolic blood pressure, diastolic dysfunction and vascular remodeling. However, resveratrol alone alleviated cardiac fibrosis and some of the functional abnormalities in SHRs. And a combination of resveratrol with hydralazine was more effective than resveratrol or hydralazine alone in improving overall cardiovascular parameters.
authors.affiliation: 1] Heart Failure Research Laboratory, Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Research Centre, Winnipeg, Manitoba, Canada [2] Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Sijo Joseph
authors.initials: SJ
authors.lastname: Thandapilly
authors.forename: Xavier Lieben
authors.initials: XL
authors.lastname: Louis
authors.forename: John
authors.initials: J
authors.lastname: Behbahani
authors.forename: Ali
authors.initials: A
authors.lastname: Movahed
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Robert
authors.initials: R
authors.lastname: Fandrich
authors.forename: Shetuan
authors.initials: S
authors.lastname: Zhang
authors.forename: Elissavet
authors.initials: E
authors.lastname: Kardami
authors.forename: Hope D
authors.initials: HD
authors.lastname: Anderson
authors.forename: Thomas
authors.initials: T
authors.lastname: Netticadan
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006332:Cardiomegaly / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D013267:Stilbenes; D006830:Hydralazine; D000077185:Resveratrol