The electrical and mechanical responses of the rabbit saphenous artery to nerve stimulation and drugs

Abstract

1 Electrical and mechanical responses to field stimulation (1-64 Hz, 0.5 ms supramaximal voltage) were recorded simultaneously in the rabbit saphenous artery. The electrical response consisted entirely of excitatory junction potentials (ej.ps) which were abolished by a, f1 methylene ATP (a,,B MeATP, 10-6 M) and by tetrodotoxin (TTX, 10-6M) but were unaffected by the ax-adrenoceptor antagonist, prazosin (10-6 M). No additional electrical response was evoked by field stimulation, even in the presence of normetanephrine (NMN) and desmethylimipramine (DMI, each 10-6M), which block neuronal and extraneuronal uptake of noradrenaline (NA) respectively. Action potentials to field stimulation were produced only in the presence of tetraethylammonium (10 3 M) which also enhanced the contraction. 2 Contractions to field stimulation were reduced (by some 50%) by prazosin (10-6M) and abolished by the additional presence of a,/ MeATP (10-6 M), which blocks purinoceptors by desensitization, suggesting the involvement of both NA and an ATP-like substance in the contractile response. 3 Idazoxan (10-6M) which blocks prejunctional a2-adrenoceptors, significantly increased the amplitude of both ej.ps and the contraction to field stimulation (10 pulses, 1-4 Hz, 0.5 ms, supramaximal voltage). 4 NA (10-2 M by pressure ejection) did not alter membrane potential even in the presence of NMN and DMI (each 10-6M). ATP (10-2M by pressure ejection) produced a concentration-dependent, a4, MeATPsensitive depolarization.

Purinergic Signaling and Blood Vessels in Health and Disease

“…At a stimulation frequency of 2 Hz, the principal transmitter is ATP, while at higher frequencies both NA and ATP are involved (Zhang and Ren, 2001). EJPs recorded in smooth muscle of the guinea pig saphenous artery were inhibited by arylazido amino propyl ATP, a P2 receptor antagonist (Cheung and Fujioka, 1986) and also by suramin (Nally and Muir, 1992). The purinergic contractile component of rabbit saphenous (and ileocolic) arteries was antagonized by nifedipine, a calcium channel blocker (Bulloch et al, 1991).…”

The purinergic neurotransmitter revisited: A single substance or multiple players?

“…For example, Sneddon & Burnstock, 1984a demonstrated that fast depolarizations in rat tail artery were resistant to α-adrenoceptor antagonists but were abolished by α,β-methylene-ATP, which was the basis to propose that ATP is a co-transmitter with NE in tail artery. Characterization of EFS-elicited EJPs in blood vessels and inhibition with P2 receptor antagonists has become a popular approach in investigating purinergic (presumably mediated by ATP) neurotransmission in numerous blood vessels including the rat tail artery (Astrand et al, 1988; Astrand & Stjarne, 1989; Stjarne & Stjarne, 1989; Jobling & McLachlan, 1992; McLaren et al, 1995; Brock & Cunnane, 1999), cutaneous arteries of isolated guinea-pig ear (Morris et al, 1998), mesenteric arteries (Muir & Wardle, 1988; Thapaliya et al, 1999; Keef et al, 1991; Haddock & Hill, 2011), and rabbit saphenous artery (Nally & Muir, 1992; see Burnstock & Ralevic, 2014). Low-frequency EFS-evoked Ca 2+ transients in smooth muscle cells in rat mesenteric small arteries are assumed to represent Ca 2+ entering smooth muscle cells through P2X1 receptors activated by ATP released from sympathetic nerves (Lamont & Wier, 2002; Lamont et al, 2006).…”

Neurotransmitter release mechanisms at the sympathetic neuroeffector junction

“…(3) EJPs can be recorded in tissues in which the noradrenaline has been depleted by pretreatment with reserpine (Burnstock & Holman, 1962b;Brock, Cunnane, Starke & Wardell, 1990) -this finding makes it most unlikely that the transmitter generating the EJP is noradrenaline; (4) EJPs are either unaltered or increased in amplitude by a-adrenoceptor antagonists and unaffected by fl-adrenoceptor antagonists (see Brock & Cunnane, 1992 a); (5) EJPs are markedly reduced in amplitude by the P2x-purinoceptor antagonists ANAPP3 (Sneddon, Westfall & Fedan, 1982) and suramin (Nally & Muir, 1992;Sneddon, 1992) or abolished after P2x-purinoceptors have been desensitized by application of the stable ATP analogue a,,8-methylene ATP (Sneddon & Burnstock, 1984 a, b); (6) brief focal application of ATP to either the rodent vas deferens or the rabbit ear artery produces a depolarization which resembles the stimulation-evoked EJP (Sneddon & Westfall, 1984;Suzuki, 1985;Cunnane & Manchanda, 1988). In these tissues focal application of noradrenaline produces no detectable alteration in membrane potential.…”