Uridine adenosine tetraphosphate and purinergic signaling in cardiovascular system: an update

Publication date: Available online 13 December 2018Source: Pharmacological ResearchAuthor(s): Zhichao Zhou, Takayuki Matsumoto, Vera Jankowski, John Pernow, S. Jamal Mustafa, Dirk J. Duncker, Daphne MerkusAbstractUridine adenosine tetraphosphate (Up4A), biosynthesized by activation of vascular endothelial growth factor receptor (VEGFR) 2, was initially identified as a potent endothelium-derived vasoconstrictor in perfused rat kidney. Subsequently, the effect of Up4A on vascular tone regulation was intensively investigated in arteries isolated from different vascular beds in rodents including rat pulmonary arteries, aortas, mesenteric and renal arteries as well as mouse aortas, in which Up4A produces vascular contraction. In contrast, Up4A produces vascular relaxation in porcine coronary small arteries and rat aortas. Intravenous infusion of Up4A into conscious rats or mice decreases blood pressure, and intravenous bolus injection of Up4A into anesthetized mice increases coronary blood flow, indicating an overall vasodilator influence in vivo. Although Up4A is the first dinucleotide described that contains both purine and pyrimidine moieties, its cardiovascular effects are exerted mainly through activation of purinergic receptors. These effects not only encompass regulation of vascular tone, but also endothelial angiogenesis, smooth muscle cell proliferation and migration, and vascular calcification. Furthermore, this review discusses a potential role for Up4A in cardiovascula...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research