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Cardiovascular consequences of conjugate bases accumulating alongside H\n                      <jats:sup>+<\/jats:sup>\n                      remain unclear. Here, we evaluate the cardiovascular effects of nine prominent carboxylates\u2014particularly lactate, 3\u2010hydroxybutyrate, and butyrate\u2014linked to metabolic and microbial activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Comparing the actions of pH\u2010adjusted Na\u2010carboxylates 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\u00a0vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The tested carboxylates generally relax arteries and veins. L\u2010lactate relaxes human and rat arteries up to 70% (EC\n                      <jats:sub>50<\/jats:sub>\n                      \u2009=\u200910.1\u2009mM) and rat brachial and mesenteric veins up to 30% of pre\u2010contractions, 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\u2010lactate shows only minor actions. In isolated perfused hearts, 10\u2009mM\u2009L\u2010lactate increases coronary flow (17.1\u2009\u00b1\u20097.7%) and left ventricular developed pressure (10.1\u2009\u00b1\u20093.0%) without affecting heart rate. L\u2010lactate infusion in rats\u2014reaching 3.7\u2009\u00b1\u20090.3\u2009mM in the circulation\u2014increases left ventricular end\u2010diastolic volume (11.3\u2009\u00b1\u20092.8%), stroke volume (22.6\u2009\u00b1\u20093.0%), cardiac output (23.4\u2009\u00b1\u20093.5%), and ejection fraction (10.6\u2009\u00b1\u20092.0%), and lowers systemic vascular resistance (34.1\u2009\u00b1\u20093.7%) without influencing blood pressure or heart rate. The ketone body 3\u2010hydroxybutyrate causes lactate accumulation and elevates left ventricular end\u2010diastolic volume in\u00a0vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Carboxylate metabolites generally relax arteries and veins. L\u2010lactate 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\u2010lactate optimizes cardiovascular function during metabolic disturbances.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70037","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T11:30:44Z","timestamp":1743593444000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Lactate orchestrates metabolic hemodynamic adaptations through a unique combination of venocontraction, artery relaxation, and positive inotropy"],"prefix":"10.1111","volume":"241","author":[{"given":"Casper","family":"Homilius","sequence":"first","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Seefeldt","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Cardiology Aarhus 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