In conditions of inadequate oxygen supply induced by a mismatch between blood flow and metabolic demand, the exercise pressor reflex (EPR) adjusts the circulation to increase oxygen delivery to the contracting skeletal muscles (Kaufman & Hayes, 2002; O'Leary et al., 1999). It is well documented that the reflex evokes increases in sympathetic activity to the heart and skeletal muscles, resulting in increases in blood pressure (BP), heart rate (HR), and total peripheral resistance (TPR) via peripheral vasoconstriction (Grotle et al., 2020; McCloskey & Mitchell, 1972; Mitchell et al., 1983). The afferent arm of the reflex consists of group III and IV skeletal muscle afferents (Kaufman et al., 1983). The group III afferents are activated mainly by mechanical stimuli at the onset of muscle contraction and group IV afferents respond predominantly to accumulated metabolites during exercise (Kaufman et al., 1983; O'Leary et al., 1999). The cardiovascular adjustments induced by the mechanically sensitive and metabolically sensitive components are known as the muscle mechanorelfex and muscle metaboreflex (MMR), respectively.
Although the EPR plays an important role in regulating cardiovascular responses to exercise, there is abnormal physiological responses in individuals with hypertension, obesity, heart failure, and peripheral artery disease (Hammond et al., 2001; Lee et al., 2020; Mitchell, 2017; Muller et al., 2012). Particularly, exaggerated BP response to exercise is a prognostic indicator of cardiovascular disease risks such as hypertension, myocardial infarction, and stroke in individuals in an absence of coronary disease (Laukkanen & Kurl, 2012; Nakashima et al., 2004). Even though pathophysiology of exercise-induced hypertension response has not been fully elucidated, plausible mechanisms to explain this phenomenon is associated with an exaggerated increase in sympathetic activity, endothelial dysfunction, arterial stiffness, and increased angiotensin II concentration (Delaney et al., 2010; Kim et al., 2020; Qin & Li, 2020; Tzemos et al., 2015). Accordingly, early treatment may be warranted to prevent cardiovascular adverse events.
Dietary intervention using nutritional supplements may be a potential approach for managing excessive sympathetic activity. An increase in nitric oxide (NO) bioavailability via dietary supplementation alters efferent sympathetic outflow. For example, a previous study demonstrated that acute dietary supplementation with beetroot juice reduced muscle sympathetic outflow at rest and during exercise in normotensive individuals (Notay et al., 2017). Findings suggest that dietary therapy may represent a target to reduce central sympathetic overactivation induced by the MMR during exercise.
An extract of grape seed has been manufactured via hydrolysis of specific enzymes, and the manufacturing process results in a grape seed extract (GSE) highly purified and rich in polyphenolic compounds (Meganatural BP; Polyphenolics, Madera, CA) (Shrikhande et al., 2011). Studies has demonstrated that the extract lowers BP via an increase in peripheral vasodilation and this health effect is related to the activation of endothelial nitric oxide synthase (eNOS) and, in turn, production of nitric oxide (NO) (Quiñones et al., 2014). This GSE consists of total phenolics (90–93%), gallic acid (≥ 2%), and catechins and epicatechins (≥ 5%). The ingredients of phenolic compounds are 9% monomers, 69% oligomers, and 22% polymers as measured by high-performance liquid chromatography (HPL-C). However, even though the NO is known to reduce central sympathetic output and peripheral vasoconstriction, potential beneficial effects of this extract on exercising BP response evoked by the MMR in human subjects have not been revealed. Thus, this study was hypothesized that dietary supplementation with GSE reduces the BP response to the MMR in healthy young individuals.