Cardiovascular function depends on an adequate vascular tone facilitating appropriate blood flow to individual tissues according to their needs. The tone results from the interplay between vasodilatation and vasoconstriction. Its rapid and efficient regulation is secured by many interconnected physiological mechanisms, both at the level of the vascular smooth muscle and the endothelium. The purpose of this review is to provide an update of the current knowledge on the mechanisms of physiological vasodilatation. First, two principal intracellular signaling pathways linked to the activation of protein kinases PKA and PKG are introduced. Subsequently, the role of endothelium-derived relaxing factors together with the endothelium-dependent hyperpolarization is discussed. The roles of ion channels and gap junctions in the communication between endothelium and vascular smooth muscle cells are particularly discussed. Finally, principal vasodilatory stimuli (mechanical, thermal, chemical) and their mechanisms of action are briefly introduced.

Department of Organic and Bioorganic Chemistry Faculty of Pharmacy Charles University Akademika Heyrovskeho 1203 500 05 Hradec Kralove Czech Republic

Department of Pharmacology and Toxicology Faculty of Pharmacy Charles University Akademika Heyrovskeho 1203 500 05 Hradec Kralove Czech Republic

Division of Pharmaceutics and Pharmacology College of Pharmacy Ohio State University Columbus OH USA

Frick Center for Heart Failure and Arrhythmia College of Medicine Dorothy M Davis Heart and Lung Research Institute Ohio State University Wexner Medical Center Columbus OH USA

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Pflugers Arch. 2025 Sep;477(9):1225. doi: 10.1007/s00424-025-03102-7. PubMed

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