Purinoceptors in the pulmonary circulation of the rat and their role in hypoxic vasoconstriction

Abstract

1 P2-purinoceptors have been characterized in the systemic circulation of a variety of species but little is known about their nature in the pulmonary vasculature. 2 In the isolated, blood perfused and ventilated lung of the rat the P2X selective analogues a,xjmethylene ATP(a,fi-meATP) (25 pg) and fi,y-methylene ATP (400 pg) caused a rise in pulmonary artery pressure (127 + 32% and 110 + 23% increase respectively, n = 6), demonstrating the existence of vasoconstrictor P2 receptors in the pulmonary circulation.3 Repeated boluses of a,#-meATP resulted in complete desensitization of the constrictor response to fi,y-meATP, but a small vasodilator response remained indicating unopposed stimulation of P2y receptors. The desensitization by a,#-meATP had no effect on angiotensin II-induced vasoconstriction.4 After desensitization of the vasoconstrictor P2 receptors with a,#-meATP, hypoxic pulmonary vasoconstriction remained intact, indicating that these receptors are not involved in this response.

ATP-induced mitogenesis is mediated by cyclic AMP response element-binding protein-enhanced TRPC4 expression and activity in human pulmonary artery smooth muscle cells

“…6). Maintenance of sufficient Ca 2ϩ within the SR is also required for cell growth, and depletion of the SR Ca 2ϩ store induces growth arrest (27,54) and triggers apoptosis (26 (37,38,56). In hypoxia-mediated pulmonary hypertension, for example, extensive pulmonary vascular remodeling can occur in addition to increased vasoconstriction, with both elements contributing to increased PVR and PAP.…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…In the isolated, blood-perfused and ventilated rat lung, P2X receptors activated by a,b-meATP caused vasoconstriction, whereas P2Y receptors, probably largely located on the endothelium, mediated a small vasodilator response (Liu et al, 1989;McCormack et al, 1989a). Vasoconstriction of the rat pulmonary vascular bed was elicited equipotently by ATP, UTP, and UDP; contractions to UTP and UDP were resistant to suramin antagonism, whereas those to ATP were blocked and so were probably mediated by P2Y 4 and P2Y 6 receptors on smooth muscle.…”

Identification of Contractile P2Y1, P2Y6, and P2Y12Receptors in Rat Intrapulmonary Artery Using Selective Ligands

“…Nucleotides also act at smooth muscle P2X and P2Y receptors to evoke pulmonary vasoconstriction (Liu et al, 1989a,b;McCormack et al, 1989;Hasséssian and Burnstock, 1995;Rubino and Burnstock, 1996;Hartley et al, 1998;Rubino et al, 1999;Chootip et al, 2002Chootip et al, , 2005Jernigan et al, 2006;Syed et al, 2010;Mitchell et al, 2012). These effects are likely to become more pronounced in conditions where endothelium-dependent relaxation is impaired, such as hypoxiaor monocrotaline-induced pulmonary hypertension (Adnot et al, 1991;Mam et al, 2010) and chronic obstructive pulmonary disease (Dinh-Xuan et al, 1991).…”