Effects of tyramine on noradrenaline outflow and electrical responses induced by field stimulation in the perfused rabbit ear artery

Abstract

In the perfused rabbit ear artery the basal outflows of noradrenaline (NA) and 3,4‐dihydroxyphenylglycol (DOPEG) were < 1 ng g−1 and 1–2 ng g−1 wet weight of tissue respectively. Field stimulation increased outflows of NA and DOPEG in a frequency‐dependent manner, and they reached the maximum value at frequencies over 5 Hz. Tyramine (1 × 10−6 − 1 × 10−4 M) increased basal outflow of NA and DOPEG, in a dose‐dependent manner. This effect was not blocked by tetrodotoxin (TTX, 3 × 10−7 M), but was prevented by pretreatment with 6‐hydroxydopamine (6‐OHDA). Tyramine increased the field stimulation‐induced outflow of NA but not that of DOPEG in a dose‐dependent manner. Cocaine (1 × 10−5 M) reduced the increased outflow of NA induced by tyramine at rest and during field stimulation, without modifying DOPEG‐outflow. Guanethidine (5 × 10−6 M), increased outflows of NA and DOPEG at rest, and reduced the NA outflow induced by field stimulation. Pretreatment with guanethidine (5 × 10−6 M) did not block the action of tyramine on NA and DOPEG basal outflows. Additional application of guanethidine during the presence of tyramine did reduce the outflow of NA induced by field stimulation, but did not modify the outflow of NA and DOPEG at rest. Tyramine at concentrations over 1 × 10−5 M depolarized the smooth muscle membrane of the rabbit ear artery. After chemical denervation with 6‐hydroxydopamine (6‐OHDA) the depolarizing action of tyramine was reduced. Tyramine‐induced depolarization was attenuated by prazosin (5 × 10−6 M) or phentolamine (5 × 10−6 M), but not by guanethidine (5 × 10−6 M). In 6‐OHDA‐denervated tissues, tyramine‐induced depolarization was attenuated by phentolamine but not by prazosin. Field stimulation evoked excitatory junction potential (e.j.p.), slow depolarization and spike potential in the rabbit ear artery. Tyramine reduced, while guanethidine blocked these electrical responses. Tyramine did not alter the facilitation process of e.j.ps. In tissues pretreated with guanethidine, tyramine evoked either no electrical response or a slow depolarization during field stimulation. The slow depolarization was blocked by prazosin. Tyramine reduced the NA content of tissues in a dose‐dependent manner (by 31% at 10−4 M). Guanethidine (5 × 10−6 M) reduced the NA content by 20%. We conclude that in the rabbit ear artery, tyramine depolarizes the smooth muscle membrane indirectly by releasing neuronal NA which acts on α‐adrenoceptors, and directly by an action on the smooth muscle cells. Two NA compartments (guanethidine‐sensitive and tyramine‐sensitive NA) could be identified. Field stimulation releases the former with associated generation of e.j.p. and slow depolarization whilst the release of the latter is not accompanied by e.j.p. generation.

Differences in α1-Adrenoceptor Subtype-Mediated Vasoconstriction by Tyramine and Nerve Stimulation in Canine Splenic Artery

“…The first phase may contain mostly a P2X receptor-mediated purinergic component and the second phase, mainly an α 1 -adrenoceptormediated adrenergic component (20). Tyramine is capable of facilitating outflow of noradrenaline during nerve excitation, in addition to an increase in the basal outflow of noradrenaline (3). In the present study, we were able to confirm that tyramine facilitated the second phase of double peaked vasoconstrictions, but having little effect on the first one.…”

“…The subtype of α-adrenoceptors involved in the tyramine-induced response was generally recognized to be an α 1 -adrenoceptor subtype in many blood vessels (3,5). Several lines of evidence have suggested that there is heterogeneity of α 1 -adrenoceptor subtypes located in the neuroeffector junction and extrajunctional region (6 -9).…”

Heterogeneous distribution of muscarinic receptors in the rabbit saphenous artery

“…The ej.p. is resistant to aadrenoceptor antagonists, but can be blocked by guanethidine or chemical denervation of adrenergic nerves by 6-hydroxydopamine (Miyahara & Suzuki, 1985), thereby indicating that this potential may be generated by substances released from perivascular adrenergic nerves. By comparing the ej.p.…”

Influence of calcium-entry blockade on vasoconstrictor responses in feline mesenteric vascular bed.

“…2 " 7 It has been shown in in vivo studies that pressor responses to exogenous and neurogenically released norepinephrine may be mediated by different a-adrenoceptor subtypes. 38 " 10 In the canine hind limb and the pithed rat, responses to sympathetic nerve stimulation are selectively blocked by a,-adrenoceptor antagonists, but responses to exogenous norepinephrine are attenuated by a 2 -adrenoceptor antagonists.…”

“…Tyramine is an indirect acting amine that displaces norepinephrine from adrenergic terminals by a calcium-independent process. 3435 Although tyramine may possess some direct activity, 38 vasoconstrictor responses to this agent are mainly indirect in the feline mesenteric vascular bed because they are almost entirely blocked by cocaine, an agent that blocks neuronal uptake of norepinephrine. 34 -39 Although yohimbine reduced responses to tyramine by approximately 50%, the effects of this agent on responses to electrical stimulation of the sympathetic by guest on May 11, 2018 http://circres.ahajournals.org/ Downloaded from nerves are difficult to interpret since presynaptic and postsynaptic blocking actions of the antagonist would be expected to have opposing effects on the pressor response.…”