Lactate orchestrates metabolic hemodynamic adaptations through a unique combination of venocontraction, artery relaxation, and positive inotropy

AIM: remain unclear. Here, we evaluate the cardiovascular effects of nine prominent carboxylates-particularly lactate, 3-hydroxybutyrate, and butyrate-linked to metabolic and microbial activity. METHODS: Comparing the actions of pH-adjusted Na-carboxylates to equiosmolar NaCl, we study arteries and veins isolated from healthy rats and humans with ischaemic heart disease, isolated perfused rat hearts, and rat cardiovascular function in vivo. RESULTS: = 10.1 mM) and rat brachial and mesenteric veins up to 30% of pre-contractions, yet stands out by augmenting contractions of rat femoral, saphenous, and lateral marginal veins and human internal thoracic and great saphenous veins up to 50%. D-lactate shows only minor actions. In isolated perfused hearts, 10 mM L-lactate increases coronary flow (17.1 ± 7.7%) and left ventricular developed pressure (10.1 ± 3.0%) without affecting heart rate. L-lactate infusion in rats-reaching 3.7 ± 0.3 mM in the circulation-increases left ventricular end-diastolic volume (11.3 ± 2.8%), stroke volume (22.6 ± 3.0%), cardiac output (23.4 ± 3.5%), and ejection fraction (10.6 ± 2.0%), and lowers systemic vascular resistance (34.1 ± 3.7%) without influencing blood pressure or heart rate. The ketone body 3-hydroxybutyrate causes lactate accumulation and elevates left ventricular end-diastolic volume in vivo. CONCLUSION: Carboxylate metabolites generally relax arteries and veins. L-lactate relaxes arteries, lowering systemic vascular resistance, causes preferential venocontraction with increased ventricular diastolic filling, and elevates cardiac contractility and cardiac output. We propose that L-lactate optimizes cardiovascular function during metabolic disturbances.