Nerve evoked P2X receptor contractions of rat mesenteric arteries; dependence on vessel size and lack of role of L‐type calcium channels and calcium induced calcium release

Abstract

1 Contractile responses to short trains of nerve stimulation have been characterized in small, medium and large arteries from the rat mesenteric circulation (5th ± 6th, 2nd ± 3rd and 1st order, respectively). In addition, sources of calcium for smooth muscle contraction have been investigated. 2 Nerve stimulation (10 pulses at 10 Hz) evoked reproducible contractions. The P2 receptor antagonist suramin (100 mM) reduced constrictions by 65.3+7.4, 82.7+3.3 and 3.1+6.1% in small, medium and large arteries respectively. The a-adrenoceptor antagonist prazosin (0.1 mM) reduced responses by 32.6+2.6, 27.0+1.5 and 97.0+1.9% respectively. 3 The L-type calcium channel antagonist nifedipine (1 mM) reduced nerve-evoked contractions by 2.8+3.3, 10.0+3.7 and 13.5+2.7% in small, medium and large arteries respectively. When the adrenergic component of contraction was blocked by prazosin (0.1 mM) nifedipine reduced responses by 4.6+7.9, 14.3+2.0 and 3.0+1.9% respectively. 4 Contractile responses to exogenous a,b-meATP were una ected by the depletion of calcium stores with cyclopiazonic acid (30 mM). This indicates that mobilization of calcium from internal stores is not required for P2X receptor mediated smooth muscle contraction. 5 We conclude that for neurogenic responses, the P2X receptor mediated component of constriction dominates in small mesenteric arteries (3rd ± 6th order) while in large arteries (1st order) noradrenaline mediates contraction. For P2X receptor mediated responses all the calcium required for smooth muscle contraction enters the cell directly through P2X receptor channels.

P2X1 Receptor-Deficient Mice Establish the Native P2X Receptor and a P2Y6-Like Receptor in Arteries

“…In the present study, the purinergic component accounted for ϳ50% of the neurogenic response. These stimulation conditions, i.e., a long train of stimulation, have been shown to favor adrenergic transmission, and shorter bursts of stimulation correspond more closely to those recorded under physiological conditions; in resistance arteries, the purinergic component dominates under these conditions (Ramme et al, 1987, Gitterman andEvans, 2001). The characterization of the underlying P2X 1 receptor response to applied agonists and the abolition of P2X receptor-mediated vasoconstriction to agonist application or nerve stimulation in mesenteric arteries from P2X 1 receptor-deficient mice demonstrate that the P2X 1 receptor underlies a significant component of the neurogenic vasoconstriction.…”

“…Antagonists were superfused for 15 min before being applied concomitantly with the agonist. Trains of electrical-field stimulation (100 pulses at 10 Hz, 50V, 0.25-ms pulse width) were given at 5-min intervals as described previously (Gitterman and Evans, 2001). Electrically evoked constrictions were reversibly abolished by treatment with tetrodotoxin (0.3 M), demonstrating that they resulted from nerve stimulation.…”

“…ATP is costored and coreleased with noradrenaline from sympathetic nerves, mediates vasoconstriction through artery P2X receptors (Burnstock, 1997), and can account for up to 65 to 100% of the neurogenic response in resistance arteries (Ramme et al, 1987;Gitterman and Evans, 2001). ATP is also released from endothelial (Dubyak, 2002) and blood cells or because of local tissue damage (Burnstock, 1997) and can produce vasoconstriction through the stimulation of P2X and P2Y receptors (Ralevic and Burnstock, 1998).…”

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

“…Intracellular ATP is an essential molecular energy source, while extracellular ATP, which can be released from vascular endothelial cells (44,71), damaged vessel walls (4), hypoxic myocardium (15), and aggregating platelets (29), serves as a potent vasoconstrictor (20,24) and smooth muscle and endothelial cell mitogen (7,19). ATP also can be released from perivascular nerves as an excitatory neurotransmitter (6).…”

Purinergic Signaling in Cardiovascular System: A Fertile Ground of Investigation

“…Importantly, the activation of endothelial P2 receptors induces a local vasorelaxation by the release of nitric oxide (NO), prostacyclin (PGI2) and endothelium-derived hyperpolarizing factor (EDHF) [6]. In an opposite way, the VSMC purinoceptors activation promotes a vasoconstriction via P2 and P2Y [7]. A broad range of studies has showing the importance of purines in the cardiovascular regulation.…”