NTPDase1 (CD39) controls nucleotide-dependent vasoconstriction in mouse

• Published in: Cardiovascular research Vol. 85; no. 1; pp. 204 - 213
• Main Authors: Kauffenstein, Gilles, Drouin, Annick, Thorin-Trescases, Nathalie, Bachelard, Hélène, Robaye, Bernard, D'Orléans-Juste, Pedro, Marceau, François, Thorin, Éric, Sévigny, Jean
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.01.2010
• Subjects: Animals; Antigens, CD - physiology; Aorta - physiology; Apyrase - physiology; Biological and medical sciences; Blood Pressure - drug effects; Cardiology. Vascular system; CD39; In Vitro Techniques; Medical sciences; Mice; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - enzymology; Myocytes, Smooth Muscle - enzymology; Myogenic tone; NTPDase1; Nucleotides - pharmacology; P2Y receptor; Receptors, Purinergic - analysis; Receptors, Purinergic - physiology; Smooth muscle cell; UDP; Uridine Diphosphate - pharmacology; UTP; Vasoconstriction; Vasoconstriction - drug effects; UTP; UDP; Smooth muscle cell; Myogenic tone; P2Y receptor; Vasoconstriction; CD39; NTPDase1; Rodentia; Check; Smooth muscle; Phlebology; Prevention; Vertebrata; Control; Mammalia; P2Y purinergic receptor; Mouse; Animal; Nucleotide; Circulatory system; Cardiology; Cell
• ISSN: 0008-6363; 1755-3245; 1755-3245
• DOI: 10.1093/cvr/cvp265

Aims Extracellular nucleotides are vasoactive molecules. The concentrations of these molecules are regulated by ectonucleotidases. In this study, we investigated the role of the blood vessel ectonucleotidase NTPDase1, in the vasoconstrictor effect of nucleotides using Entpd1−/− mice. Methods and results Immunofluorescence, enzyme histochemistry, and HPLC analysis were used to evaluate both NTPDase expression and activity in arteries and isolated vascular smooth muscle cells (VSMCs). Vascular reactivity was evaluated in vitro and mean arterial blood pressure was recorded in anesthetized mice after nucleotide i.v. infusion. Expression of nucleotide receptors in VSMCs was determined by RT–PCR. Entpd1−/− mice displayed a dramatic deficit of nucleotidase activity in blood vessel wall in situ and in VSMCs in comparison to control mice. In aortic rings from Entpd1−/− mice, UDP and UTP induced a potent and long-lasting constriction contrasting with the weak response obtained in wild-type rings. This constriction occurred through activation of P2Y6 receptor and was independent of other uracil nucleotide-responding receptors (P2Y2 and P2Y4). UDP infusion in vivo increased blood pressure and this effect was potentiated in Entpd1−/− mice. In addition, pressurized mesenteric arteries from Entpd1−/− mice displayed an enhanced myogenic response, consistent with higher local concentrations of endogenously released nucleotides. This effect was inhibited by the P2 receptor antagonist RB-2. Conclusion NTPDase1 is the major enzyme regulating nucleotide metabolism at the surface of VSMCs and thus contributes to the local regulation of vascular tone by nucleotides.