title: Calorie restriction prevents hypertension and cardiac hypertrophy in the spontaneously hypertensive rat.
abstract: Because recent evidence demonstrated that calorie restriction (CR) has numerous beneficial cardiovascular effects, we investigated whether short-term CR could reduce hypertension and prevent cardiac hypertrophy inherent to the nonobese spontaneously hypertensive rat (SHR). After 5 weeks of either ad libitum feeding or short-term CR, SHRs subjected to short-term CR had lower systolic blood pressure (BP) and reduced left ventricular wall thickness as assessed by noninvasive tail-cuff BP measurements and echocardiography, respectively. In addition, ultrasound measurements of the femoral artery revealed that flow-mediated vasodilation was significantly improved in SHRs with CR compared to controls. Moreover, pressure myography of isolated mesenteric arteries and subsequent histological and biochemical analysis of these arteries demonstrated that short-term CR improved vascular compliance, increased endothelial nitric oxide synthase (eNOS) activity and nitric oxide bioavailability, and reduced vascular remodeling compared to ad libitum-fed SHRs. Although these effects are likely multifactorial, they were associated with elevated levels of the circulating adipokine, adiponectin, and enhanced AMP-activated protein kinase (AMPK) activity. To provide evidence that elevated adiponectin levels in the SHR is sufficient to prevent an increase in BP, adenoviral-mediated overexpression of adiponectin increased circulating levels of adiponectin, reduced BP, and activated the AMPK/eNOS pathway in the absence of CR. Overall, our findings provide compelling evidence that short-term CR exerts beneficial effects in the SHR via stimulation of an adiponectin/AMPK/eNOS signaling axis. As a result, CR may serve as an effective nonpharmacological treatment of hypertension, and targeting the adiponectin/AMPK/eNOS pathway may improve treatment of hypertension.
authors.affiliation: 458 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. jason.dyck@ualberta.ca
authors.forename: Vernon W
authors.initials: VW
authors.lastname: Dolinsky
authors.forename: Jude S
authors.initials: JS
authors.lastname: Morton
authors.forename: Tatsujiro
authors.initials: T
authors.lastname: Oka
authors.forename: Isabelle
authors.initials: I
authors.lastname: Robillard-Frayne
authors.forename: Mariel
authors.initials: M
authors.lastname: Bagdan
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
authors.forename: Christine
authors.initials: C
authors.lastname: Des Rosiers
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
authors.forename: Jason R B
authors.initials: JR
authors.lastname: Dyck
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D054392:Adipokines / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D031204:Caloric Restriction; D006332:Cardiomegaly / Q000517:prevention & control*; D005263:Femoral Artery / Q000502:physiology; D006973:Hypertension / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow / Q000502:physiology; D018709:Statistics, Nonparametric
chemical_list: D054392:Adipokines; D055372:AMP-Activated Protein Kinases