{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:39:49Z","timestamp":1759365589721,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["JCDD"],"abstract":"<jats:p>Evidence has suggested that post-exercise heart rate recovery (PHRR) is a useful tool in evaluating cardiac autonomic function. Altered cardiac autonomic function is characterized by heightened sympathetic activation and the abnormal reactivation of the parasympathetic nervous system and is associated with delayed HRR. Although grape seed extract (GSE) supplementation has been shown to increase nitric oxide production and modify sympathetic output, there is limited evidence on its potential beneficial effects on PHRR. We investigated the effect of GSE supplementation on PHRR during sympathetic overactivation induced by muscle metaboreflex activation (MMA) in young individuals. Participants were randomly assigned, via a double-blind, cross-over design, to either receive GSE (300 mg, two capsules) or PL (300 mg, two capsules), with a washout period of at least 72 h. between trials. A submaximal exercise test was performed using a cycle ergometer combined with an isometric handgrip exercise using a handgrip dynamometer and blood flow occlusion by placing a cuff over the brachial artery of the dominant arm. PHRR was measured at 5 s. intervals throughout the experiment. The PHRR was evaluated between GSE and PL at every min. for 300 s. PHRR kinetics significantly improved following GSE supplementation (74.3 \u00b1 7.5 s) compared with the PL condition (86.2 \u00b1 10.4 s). Our results suggest that GSE is effective in improving HRR kinetics during heightened sympathetic activity induced by MMA in young individuals (p = 0.034; ES = 0.4). Thus, regular treatment with GSE may provide a nonpharmacological intervention to reduce sympathetic hyperactivity in conditions where excessive sympathetic activity is consistently present.<\/jats:p>","DOI":"10.3390\/jcdd12100387","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T07:58:13Z","timestamp":1759305493000},"page":"387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Acute Grape Seed Extract Supplementation on Heart Rate Recovery in Young Individuals"],"prefix":"10.3390","volume":"12","author":[{"given":"Dae Sik","family":"Song","sequence":"first","affiliation":[{"name":"Department of Kinesiology, California Baptist University, 8432 Magnolia Avenue, Riverside, CA 92504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9743-6086","authenticated-orcid":false,"given":"William","family":"Boyer","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, California Baptist University, 8432 Magnolia Avenue, Riverside, CA 92504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9623-2353","authenticated-orcid":false,"given":"Trevor","family":"Gillum","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, California Baptist University, 8432 Magnolia Avenue, Riverside, CA 92504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2568-8852","authenticated-orcid":false,"given":"Sean","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, California Baptist University, 8432 Magnolia Avenue, Riverside, CA 92504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iltark","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, California Baptist University, 8432 Magnolia Avenue, Riverside, CA 92504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junbei","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Competitive Sports, Beijing Research Institute of Sports Science, 4 Guangcai North Road, Fengtai District, Beijing 100075, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Jae","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Engineering, California Baptist University, 8432 Magnolia Avenue, Riverside, CA 92504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, California Baptist University, 8432 Magnolia Avenue, Riverside, CA 92504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e347","DOI":"10.1161\/CIR.0000000000001209","article-title":"2024 Heart Disease and Stroke Statistics: A Report of US and Global Data from the American Heart Association","volume":"149","author":"Martin","year":"2024","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1113\/JP271869","article-title":"Translational neurocardiology: Preclinical models and cardioneural integrative aspects","volume":"594","author":"Ardell","year":"2016","journal-title":"J. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3911","DOI":"10.1113\/JP271870","article-title":"Clinical neurocardiology defining the value of neuroscience-based cardiovascular therapeutics","volume":"594","author":"Shivkumar","year":"2016","journal-title":"J. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1161\/CIRCRESAHA.114.302589","article-title":"The autonomic nervous system and heart failure","volume":"114","author":"Florea","year":"2014","journal-title":"Circ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5114\/aoms.2010.13500","article-title":"Methods of evaluation of autonomic nervous system function","volume":"6","author":"Zygmunt","year":"2010","journal-title":"Arch. Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1093\/ajh\/hpt173","article-title":"Delayed heart rate recovery is strongly associated with early and late-stage prehypertension during exercise stress testing","volume":"27","author":"Aneni","year":"2014","journal-title":"Am. J. Hypertens."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e008143","DOI":"10.1161\/JAHA.117.008143","article-title":"Prognostic Performance of Heart Rate Recovery on an Exercise Test in a Primary Prevention Population","volume":"7","author":"Sydo","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1056\/NEJM199910283411804","article-title":"Heart-rate recovery immediately after exercise as a predictor of mortality","volume":"341","author":"Cole","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/01.hjh.0000198040.47128.4c","article-title":"Autonomic imbalance and metabolic syndrome: Unravelling interactions, mechanisms and outcomes","volume":"24","author":"Grassi","year":"2006","journal-title":"J. Hypertens."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.ijcard.2016.10.057","article-title":"Methods of assessment of the post-exercise cardiac autonomic recovery: A methodological review","volume":"227","author":"Pecanha","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1113\/expphysiol.2013.073189","article-title":"The neural interaction between the arterial baroreflex and muscle metaboreflex is preserved in older men","volume":"98","author":"Greaney","year":"2013","journal-title":"Exp. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1161\/01.RES.57.3.461","article-title":"Microneurographic studies of the mechanisms of sympathetic nerve responses to static exercise in humans","volume":"57","author":"Mark","year":"1985","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1172\/JCI112841","article-title":"Differential control of heart rate and sympathetic nerve activity during dynamic exercise","volume":"79","author":"Victor","year":"1987","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13633","DOI":"10.1074\/jbc.M211231200","article-title":"N-oleoyldopamine, a novel endogenous capsaicin-like lipid that produces hyperalgesia","volume":"278","author":"Chu","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8400","DOI":"10.1073\/pnas.122196999","article-title":"An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors","volume":"99","author":"Huang","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0896-6273(02)00908-X","article-title":"p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia","volume":"36","author":"Ji","year":"2002","journal-title":"Neuron"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R385","DOI":"10.1152\/ajpregu.00129.2021","article-title":"Chronic ablation of TRPV1-sensitive skeletal muscle afferents attenuates the muscle metaboreflex","volume":"321","author":"Mannozzi","year":"2021","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31163","DOI":"10.1074\/jbc.M101607200","article-title":"Anandamide activates vanilloid receptor 1 (VR1) at acidic pH in dorsal root ganglia neurons and cells ectopically expressing VR1","volume":"276","author":"Olah","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1152\/japplphysiol.00549.2023","article-title":"Augmented sympathoexcitation slows postexercise heart rate recovery","volume":"135","author":"Boyes","year":"2023","journal-title":"J. Appl. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1152\/japplphysiol.01243.2009","article-title":"Muscle metaboreflex-induced coronary vasoconstriction functionally limits increases in ventricular contractility","volume":"109","author":"Coutsos","year":"2010","journal-title":"J. Appl. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"H1029","DOI":"10.1152\/ajpheart.00879.2012","article-title":"Muscle metaboreflex-induced coronary vasoconstriction limits ventricular contractility during dynamic exercise in heart failure","volume":"304","author":"Coutsos","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1152\/jappl.1993.74.4.1748","article-title":"Autonomic mechanisms of muscle metaboreflex control of heart rate","volume":"74","year":"1993","journal-title":"J. Appl. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1152\/japplphysiol.00139.2007","article-title":"Muscle metaboreflex-induced increases in cardiac sympathetic activity vasoconstrict the coronary vasculature","volume":"103","author":"Hammond","year":"2007","journal-title":"J. Appl. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H751","DOI":"10.1152\/ajpheart.00869.2005","article-title":"Muscle metaboreflex control of ventricular contractility during dynamic exercise","volume":"290","author":"Hammond","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"H68","DOI":"10.1152\/ajpheart.00417.2016","article-title":"Exaggerated coronary vasoconstriction limits muscle metaboreflex-induced increases in ventricular performance in hypertension","volume":"312","author":"Spranger","year":"2017","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"H59","DOI":"10.1152\/ajpheart.00163.2017","article-title":"Acute beetroot juice supplementation on sympathetic nerve activity: A randomized, double-blind, placebo-controlled proof-of-concept study","volume":"313","author":"Notay","year":"2017","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_27","unstructured":"Shrikhande, A.J., Wang, H., and Kupina, S.A. (2011). Grape Extract, Dietary Supplement Thereof, and Processes Therefor. (US Patent B2:8075929)."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1080\/17461391.2021.1923815","article-title":"Effects of chronic dietary grape seed extract supplementation on aortic stiffness and hemodynamic responses in obese\/overweight males during submaximal exercise","volume":"22","author":"Dillon","year":"2022","journal-title":"Eur. J. Sport Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1089\/jmf.2017.0133","article-title":"Grape Seed Extract Supplementation Attenuates the Blood Pressure Response to Exercise in Prehypertensive Men","volume":"21","author":"Kim","year":"2018","journal-title":"J. Med. Food"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jff.2013.11.008","article-title":"Involvement of nitric oxide and prostacyclin in the antihypertensive effect of low-molecular-weight procyanidin rich grape seed extract in male spontaneously hypertensive rats","volume":"6","author":"Guerrero","year":"2014","journal-title":"J. Funct. Foods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1249\/MSS.0000000000000573","article-title":"Mechanisms Underlying Exaggerated Metaboreflex Activation in Prehypertensive Men","volume":"47","author":"Kim","year":"2015","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s12576-019-00669-6","article-title":"Muscle sympathetic nerve activity during exercise","volume":"69","author":"Katayama","year":"2019","journal-title":"J. Physiol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1139\/apnm-2019-0645","article-title":"Effects of combined histamine H(1) and H(2) receptor blockade on hemodynamic responses to dynamic exercise in males with high-normal blood pressure","volume":"45","author":"Naylor","year":"2020","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_34","first-page":"e70010","article-title":"Effects of acute grape seed extract supplementation on muscle metaboreflex in healthy young individuals","volume":"45","author":"Apilado","year":"2025","journal-title":"Sport Sci. Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1152\/japplphysiol.00395.2014","article-title":"Heart rate recovery after maximal exercise is blunted in hypertensive seniors","volume":"117","author":"Best","year":"2014","journal-title":"J. Appl. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"H133","DOI":"10.1152\/ajpheart.00062.2007","article-title":"Parasympathetic reactivation after repeated sprint exercise","volume":"293","author":"Buchheit","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1111\/j.1365-2796.2011.02452.x","article-title":"Heart rate recovery: What now?","volume":"270","author":"Lauer","year":"2011","journal-title":"J. Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"552","DOI":"10.7326\/0003-4819-132-7-200004040-00007","article-title":"Heart rate recovery after submaximal exercise testing as a predictor of mortality in a cardiovascularly healthy cohort","volume":"132","author":"Cole","year":"2000","journal-title":"Ann. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ijcard.2010.04.079","article-title":"Effects of normal blood pressure, prehypertension, and hypertension on autonomic nervous system function","volume":"151","author":"Erdogan","year":"2011","journal-title":"Int. J. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e005505","DOI":"10.1161\/JAHA.117.005505","article-title":"Heart Rate Recovery and Risk of Cardiovascular Events and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies","volume":"6","author":"Qiu","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1001\/jama.284.11.1392","article-title":"Heart rate recovery and treadmill exercise score as predictors of mortality in patients referred for exercise ECG","volume":"284","author":"Nishime","year":"2000","journal-title":"JAMA"}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/12\/10\/387\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T08:51:41Z","timestamp":1759308701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/12\/10\/387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["jcdd12100387"],"URL":"https:\/\/doi.org\/10.3390\/jcdd12100387","relation":{},"ISSN":["2308-3425"],"issn-type":[{"value":"2308-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]}}}