Homilius Casper, Seefeldt Jacob M, Hansen Jakob, Nielsen Roni, de Paoli Frank V, Boedtkjer Ebbe
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Acta Physiol (Oxf). 2025 May;241(5):e70037. doi: 10.1111/apha.70037.
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.
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.
The tested carboxylates generally relax arteries and veins. L-lactate relaxes human and rat arteries up to 70% (EC = 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.
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.
氢离子（H⁺）促进代谢性血流调节，但对心脏收缩力有负面影响。与H⁺同时积累的共轭碱的心血管后果尚不清楚。在此，我们评估了九种主要羧酸盐——特别是乳酸盐、3-羟基丁酸盐和丁酸盐——与代谢和微生物活性相关的心血管效应。
将pH值调整后的羧酸钠盐与等渗氯化钠的作用进行比较，我们研究了从健康大鼠和患有缺血性心脏病的人类分离出的动脉和静脉、离体灌注的大鼠心脏以及大鼠体内的心血管功能。
所测试的羧酸盐通常会使动脉和静脉舒张。L-乳酸盐可使人类和大鼠动脉舒张高达70%（半数有效浓度[EC] = 10.1 mM），使大鼠肱静脉和肠系膜静脉舒张高达收缩前水平的30%，但在使大鼠股静脉、隐静脉和外侧边缘静脉以及人类胸廓内静脉和大隐静脉收缩增强高达50%方面表现突出。D-乳酸盐仅表现出轻微作用。在离体灌注心脏中，10 mM L-乳酸盐可增加冠状动脉血流量（17.1 ± 7.7%）和左心室舒张末期压力（10.1 ± 3.0%），而不影响心率。给大鼠输注L-乳酸盐——使循环中的浓度达到3.7 ± 0.3 mM——可增加左心室舒张末期容积（11.3 ± 2.8%）、每搏输出量（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%），而不影响血压或心率。酮体3-羟基丁酸盐会导致乳酸盐积累并在体内升高左心室舒张末期容积。
羧酸盐代谢产物通常会使动脉和静脉舒张。L-乳酸盐使动脉舒张，降低全身血管阻力，导致优先的静脉收缩并增加心室舒张期充盈，同时提高心脏收缩力和心输出量。我们提出L-乳酸盐在代谢紊乱期间优化心血管功能。
