Abstract
Regular intake of polyphenol-rich food has been associated with a wide variety of beneficial health effects, including the prevention of cardiovascular diseases. However, the parent flavonoids have mostly low bioavailability and, hence, their metabolites have been hypothesized to be bioactive. One of these metabolites, 3-hydroxyphenylacetic acid (3-HPAA), formed by the gut microbiota, was previously reported to exert vasorelaxant effects ex vivo. The aim of this study was to shed more light on this effect in vivo, and to elucidate the mechanism of action. 3-HPAA gave rise to a dose-dependent decrease in arterial blood pressure when administered i.v. both as a bolus and infusion to spontaneously hypertensive rats. In contrast, no significant changes in heart rate were observed. In ex vivo experiments, where porcine hearts from a slaughterhouse were used to decrease the need for laboratory animals, 3-HPAA relaxed precontracted porcine coronary artery segments via a mechanism partially dependent on endothelium integrity. This relaxation was significantly impaired after endothelial nitric oxide synthase inhibition. In contrast, the blockade of SKCa or IKCa channels, or muscarinic receptors, did not affect 3-HPAA relaxation. Similarly, no effects of 3-HPAA on cyclooxygenase nor L-type calcium channels were observed. Thus, 3-HPAA decreases blood pressure in vivo via vessel relaxation, and this mechanism might be based on the release of nitric oxide by the endothelial layer.
Highlights
Cardiovascular disease is the leading cause of death worldwide, with an estimated number of deaths approaching 18 million per year
As 3-hydroxyphenylacetic acid (3-HPAA) relaxes smooth muscle cells ex vivo [14], this study aimed to test if this metabolite is able to cause a decrease in arterial blood pressure in vivo and to detect its mechanism of action in a series of mechanistic experiments
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Summary
Cardiovascular disease is the leading cause of death worldwide, with an estimated number of deaths approaching 18 million per year. Coronary artery disease and stroke contribute to approximately 85% of these fatal cardiovascular events [1]. The global mortality and morbidity have prompted the implementation of guidelines for prevention of cardiovascular risks [2]. The detection of persistent high arterial blood pressure with subsequent treatment is among the main strategies [3,4]. Hypertension is classified as a major risk factor for cardiovascular diseases. It is mostly caused by increased systemic vascular resistance, and this is often related to various structural and functional changes in the vasculature, which disrupt vascular homeostasis. The tunica intima of blood vessels, formed by a single layer of endothelial cells, is dysfunctional. The vascular smooth muscle cells often appear more contracted and less responsive to endothelium-derived relaxing factors [5]
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