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

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 muM) reduced constrictions by 65.3 +/- 7.4, 82.7 +/- 3.3 and 3.1 +/- 6.1% in small, medium and large arteries respectively. The alpha -adrenoceptor antagonist prazosin (0.1 muM) 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 muM) 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 muM) nifedipine reduced responses by 4.6 +/- 7.9, 14.3 +/- 2.0 and 3.0 +/- 1.9% respectively. 4 Contractile responses to exogenous alpha,beta -meATP were unaffected by the depletion of calcium stores with cyclopiazonic acid (30 muM). 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.