1038 H ypertension is an important and modifiable risk fac- tor for cardiovascular disease, affecting ≈1 in 4 adults worldwide. 1 In the United States, hypertension is estimated to account for >$46 billion annually in healthcare services, medi- cation, and lost productivity, 2 and these costs are expected to increase substantially over the coming decades. A universal consensus is that prevention, rather than treatment, is a more strategic and cost-effective approach to reducing the burden of cardiovascular disease in coming decades. Essential hypertension, in which known primary causes (eg, renovascular disease, pheochromocytoma, monogenic causes, etc) are not present, makes up 95% of hypertension worldwide. 3 Although the pathogenesis of essential hyperten- sion is multifactorial and complex, subclinical changes in vas- cular function often precede the development of hypertension and circulatory decline. 4 The spontaneously hypertensive rat (SHR) is a model of essential hypertension in which blood pressure (BP) begins to rise after 6 weeks of age, ultimately reaching stable pressures of ≈180 to 200 mm Hg. Recently, Komolova et al reported evidence of altered vascular resis- tance profiles and renal hemodynamics as early as 3 weeks of age in the SHR, 5 implicating these early functional changes as a cause, rather than a consequence, of hypertension in this model. As such, the developmental period before weaning (ie, See Editorial Commentary, pp 829–830 Abstract—This study was undertaken to determine whether perinatal maternal resveratrol (Resv)—a phytoalexin known to confer cardiovascular protection—could prevent the development of hypertension and improve vascular function in adult spontaneously hypertensive rat offspring. Dams were fed either a control or Resv-supplemented diet (4 g/kg diet) from gestational day 0.5 until postnatal day 21. Indwelling catheters were used to assess blood pressure and vascular function in vivo; wire myography was used to assess vascular reactivity ex vivo. Perinatal Resv supplementation in dams had no effect on fetal body weights, albeit continued maternal treatment postnatally resulted in growth restriction in offspring by postnatal day 21; growth restriction was no longer evident after 5 weeks of age. Maternal perinatal Resv supplementation prevented the onset of hypertension in adult offspring (-18 mm Hg; P=0.007), and nitric oxide synthase inhibition (with L-NG-nitroarginine methyl ester) normalized these blood pressure differences, suggesting improved nitric oxide bioavailability underlies the hemodynamic alterations in the Resv-treated offspring. In vivo and ex vivo, vascular responses to methylcholine were not different between treatment groups, but prior treatment with L- NG-nitroarginine methyl ester attenuated the vasodilation in untreated, but not Resv-treated adult offspring, suggesting a shift toward nitric oxide–independent vascular control mechanisms in the treated group. Finally, bioconversion of the inactive precursor big endothelin-1 to active endothelin-1 in isolated mesenteric arteries was reduced in Resv-treated offspring (-28%; P<0.05), and this difference could be normalized by L-NG-nitroarginine methyl ester treatment. In conclusion, perinatal maternal Resv supplementation mitigated the development of hypertension and causes persistent alterations in vascular responsiveness in spontaneously hypertensive rats. (Hypertension. 2016;67:1038-1044. DOI: 10.1161/HYPERTENSIONAHA.115.06793.) • Online Data Supplement Key Words: developmental programming ■ hypertension ■ nitric oxide ■ prevention ■ resveratrol ■ spontaneously hypertensive rat ■ vascular function Received November 9, 2015; first decision November 23, 2015; revision accepted January 5, 2016. From the Department of Obstetrics and Gynecology (A.S.C., S.T.D.), Department of Pediatrics (M.M.S., J.R.B.D.), Department of Anesthesiology and Pain Medicine (S.P., F.S.G., S.L.B.), Department of Pharmacology (J.R.B.D., S.L.B.), Cardiovascular Research Centre (A.S.C., M.M.S., F.S.G., J.R.B.D., S.T.D., S.L.B.), Women and Children’s Health Research Institute (A.S.C., M.M.S., F.S.G., J.R.B.D., S.T.D., S.L.B.), University of Alberta, Edmonton, Alberta, Canada; and Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia (A.S.C.). The online-only Data Supplement is available with this article at http://hyper.ahajournals.org/lookup/suppl/doi:10.1161/HYPERTENSIONAHA. 115.06793/-/DC1. Correspondence to Stephane Bourque, Department of Anesthesiology & Pain Medicine, 3-020H Katz Group Centre for Pharmacy and Health Research, University of Alberta, Edmonton, Alberta, T6G2E1, Canada. E-mail sbourque@ualberta.ca Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring Alison S. Care, Miranda M. Sung, Sareh Panahi, Ferrante S. Gragasin, Jason R.B. Dyck, Sandra T. Davidge, Stephane L. Bourque © 2016 American Heart Association, Inc. Hypertension is available at http://hyper.ahajournals.org DOI: 10.1161/HYPERTENSIONAHA.115.06793 Developmental Programming at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from at University of Alberta on July 3, 2016 http://hyper.ahajournals.org/ Downloaded from