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

IF 5.6 2区医学 Q1 PHYSIOLOGY

Acta Physiologica Pub Date : 2025-04-01 DOI:10.1111/apha.70037

Casper Homilius, Jacob M. Seefeldt, Jakob Hansen, Roni Nielsen, Frank V. de Paoli, Ebbe Boedtkjer

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Abstract

Aim

H⁺ facilitates metabolic blood flow regulation while negatively impacting cardiac contractility. Cardiovascular consequences of conjugate bases accumulating alongside H⁺ 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

The tested carboxylates generally relax arteries and veins. L-lactate relaxes human and rat arteries up to 70% (EC₅₀ = 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.

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乳酸通过独特的静脉收缩、动脉舒张和正性肌力调节代谢血液动力学适应

目的 H+ 在促进代谢血流调节的同时，也对心脏收缩力产生负面影响。与 H+ 同时积聚的共轭碱对心血管的影响尚不清楚。在此，我们评估了九种主要羧酸盐（尤其是乳酸、3-羟基丁酸盐和丁酸盐）对心血管的影响，这些影响与代谢和微生物活动有关。方法我们对从健康大鼠和患有缺血性心脏病的人体内分离出的动脉和静脉、分离灌注的大鼠心脏以及大鼠体内的心血管功能进行了研究，比较了经 pH 调整的 Na 羧酸盐和等体积氯化钠的作用。结果测试的羧酸盐一般都能松弛动脉和静脉。L 型乳酸盐能使人和大鼠动脉松弛达 70%（EC50 = 10.1 mM），使大鼠肱静脉和肠系膜静脉松弛达收缩前的 30%，但它能使大鼠股静脉、隐静脉和侧缘静脉以及人胸内静脉和大隐静脉的收缩增强达 50%。D-乳酸仅有轻微作用。在离体灌注心脏中，10 mM L-乳酸盐可增加冠状动脉流量（17.1 ± 7.7%）和左心室显像压力（10.1 ± 3.0%），而不影响心率。左旋乳酸在大鼠循环中的浓度达到 3.7 ± 0.3 毫摩尔时，可增加左心室舒张末期容积（11.3 ± 2.8%）、每搏量（22.6 ± 3.0%）、心输出量（23.4 ± 3.5%）和射血分数（10.6 ± 2.0%），并降低全身血管阻力（34.1 ± 3.7%），但不会影响血压或心率。酮体 3-hydroxybutyrate 会导致乳酸积聚，并增加体内左心室舒张末期容积。结论羧酸代谢物通常能松弛动脉和静脉。左旋乳酸可松弛动脉，降低全身血管阻力，导致静脉优先收缩，增加心室舒张充盈，提高心脏收缩力和心排血量。我们认为，左旋乳酸可在代谢紊乱时优化心血管功能。

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来源期刊

Acta Physiologica 医学-生理学

CiteScore

11.80

自引率

15.90%

发文量

182

审稿时长

4-8 weeks

期刊介绍： Acta Physiologica is an important forum for the publication of high quality original research in physiology and related areas by authors from all over the world. Acta Physiologica is a leading journal in human/translational physiology while promoting all aspects of the science of physiology. The journal publishes full length original articles on important new observations as well as reviews and commentaries.