Adrenergic transmission in the dog mesenteric vein and its modulation by α‐adrenoceptor antagonists

1 A study was made of the subtypes of postjunctional a-adrenoceptors which mediate arterial and venous constriction in the hindquarters circulation of anaesthetized cats, as measured by changes in perfusion pressure and vena cava blood flow, respectively. 2 It was found that, while noradrenaline caused constriction in both the arterial and venous compartments, methoxamine caused only arterial constriction. Clonidine and B-HT 920 also caused arterial and venous constriction although autodesensitization to both drugs occurred. 3 The ability of either prazosin or yohimbine to antagonize the constrictor effects of noradrenaline was also examined. It was found that the combination of both antagonist drugs abolished both the arterial and venous constrictor effects of noradrenaline. However, there was a greater prazosinresistant response to noradrenaline in the venous compartment as compared with the arterial effects of noradrenaline. Yohimbine caused approximately equal reductions in the effect of noradrenaline in both arteries and veins, which was greater than that observed with prazosin. 4 These results suggest that, in the cat hindquarters, both a,-and a2-adrenoceptors are present in the arterial circulation, whereas there are mainly a2-adrenoceptors in the venous circulation.

Section: Discussionsupporting

confidence: 54%

Postjunctional α₂‐adrenoceptors mediate venoconstriction in the hindquarters circulation of anaesthetized cats

Bentley

Widdop

1987

“…with the slow depolarization which may be generated by NA, the ej.p. could be used as an indicator of the amount of NA released during perivascular nerve stimulation (Suzuki, 1984;Suzuki et al, 1984). The present experiments demonstrated that in the rabbit saphenous artery ACh inhibited the amplitude of the ej.p., as has been demonstrated in the guinea-pig mesenteric artery (Kuriyama & Suzuki, 1981).…”

Section: Ach-induced Hyperpolarization Ofsmooth Muscle Membranementioning

confidence: 73%

Heterogeneous distribution of muscarinic receptors in the rabbit saphenous artery

Komori

Suzukixys

1987

1 The properties of the muscarinic receptors in the rabbit saphenous artery were determined from electrical and mechanical responses of smooth muscle cells produced by acetylcholine (ACh). The inhibitory action of atropine and pirenzepine on the ACh-induced responses was also studied. 5 The excitatory junction potential (ej.p.) evoked by perivascular nerve stimulation was inhibited by ACh (above 10-8 M). The ACh-induced inhibition of the ej.p. was antagonized by atropine more preferentially than by pirenzepine (the ID5o values were 3 x 10-8M for atropine and 6 x 10-6 M for pirenzepine).6 It is concluded that in the rabbit saphenous artery, two subtypes of muscarinic receptor (M, and M2) are located on the endothelial cells. Stimulation of each subtype releases a different substance, i.e., a hyperpolarizing substance (M,-subtype) or a relaxant substance (M2-subtype). In prejunctional nerve terminals, the muscarinic receptors responsible for inhibiting the release of transmitter substances are of the M2-subtype.

“…amplitude and depresses the facilitation process of e.j.ps in the guinea-pig mesenteric artery (Kuriyama & Makita, 1983). However, in the rabbit saphenous or ear arteries (Holman & Surprenant, 1980) and in the dog mesenteric vein (Suzuki, 1984), the decrease in e.j.p. amplitude during NA application is not prevented by ca-adrenoceptor antagonists which possess higher selectivity for the CX2-subtype.…”

Section: Discussionmentioning

confidence: 90%

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

Miyahara

Suzuki

1985

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.