Indole‐3‐propionic Acid, Bacterial Metabolite of Tryptophan, Increases Blood Pressure in Normotensive and Hypertensive Rats

Tryptophan is an exogenous amino acid, undergoing complex metabolism in mammals, including formation of gut microbiota-derived metabolites. Tryptophan was proven to increase blood pressure in rats and humans, however; it has not been profoundly investigated, whether its impact on cardiovascular system might be due to the action of microbiota derived indoles, especially indole-3-propionic acid (IPA). Acute hemodynamic experiments were performed on 12-week-old Wistar-Kyoto (WKY) and 16-week-old Spontaneously-Hypertensive (SHR) male anesthetized rats. Mean arterial blood pressure (MABP) and heart rate (HR) were evaluated for 120 minutes after intravenous infusion of 10% DMSO (Vehicle) and IPA in increasing doses (1.6-53 µM/kg body wt). In separate series of experiments impact of IPA on vascular contractility was evaluated in ex vivo experiments performed on mesenteric resistance arteries (MRAs). IPA increased significantly blood pressure in normotensive and hypertensive rats. In normotensive rats at highest dose IPA revealed less pronounced hypertensive effect, accompanied by decrease in HR. This effect was not observed in hypertensive rats, where IPA increased MABP in dose dependent matter, with concomitant tachycardic response. In ex vivo experiments IPA increased contractility of endothelium-denuded MRAs and reduced acetylcholine-dependent dilatation of MRAs. Our study suggest, that IPA takes part in regulation of blood pressure, by revealing hypertensive and vasoconstrictive activity. These effects are in line with actions of its precursor tryptophan, suggesting important role of bacterial metabolism of tryptophan in its cardiovascular effects.