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

Abstract

The subtypes of postjunctional a-adrenoceptors activated by neuronally released and exogenous norepinephrine and the source of calcium used for vasoconstrictor responses were investigated in the feline mesenteric vascular bed. Under constant flow conditions, intra-arterial injections of phenylephrine and UK14304, a,-and a 2 -adrenoceptor agonists, increased mesenteric arterial perfusion pressure in a dose-related manner. Prazosin, an a,-antagonist, reduced vasoconstrictor responses to phenylephrine without altering responses to UK14304. Yohimbine, an a 2 -antagonist, reduced responses to UK 14304 without altering responses to phenylephrine. The same pattern of blockade was observed in animals pretreated with 6-hydroxydopamine to destroy the integrity of adrenergic terminals. Responses to phenylephrine and UK 14304 were reduced by nitrendipine, a calcium-entry blocking agent, and this agent decreased vasoconstrictor responses to sympathetic nerve stimulation, tyramine, and norepinephrine. Responses to sympathetic nerve stimulation were selectively blocked by prazosin, but responses to norepinephrine were selectively blocked by yohimbine. Vasoconstrictor responses to tyramine were reduced by both prazosin and yohimbine. Nitrendipine also reduced responses to angiotensin II, U46619, a prostaglandin endoperoxide analogue, Bay K 8644, and potassium chloride. These data suggest the presence of a,-and postjunctional a 2 -adrenoceptors and support the hypothesis that norepinephrine released by nerve excitation acts mainly on a,-receptors but that exogenous norepinephrine acts primarily on a 2 -receptors. However, norepinephrine released by tyramine acts on both receptor subtypes. Nitrendipine inhibited responses to the a,-and a 2 -adrenoceptor agonists as well as those to nerve released and exogenous norepinephrine, the calcium agonist, Bay K 8644, and to other vasoconstrictor agents. These data suggest that in the feline mesenteric vascular bed, an extracellular source of calcium ions is required for vasoconstriction induced by a variety of mechanisms including activation of a,-and postjunctional a 2 -adrenoceptors.

Differential effects of calcium antagonists and Bay K 8644 on contractile responses to exogenous noradrenaline and adrenergic nerve stimulation in the rabbit ear artery

“…In line with this notion, experimental studies on pithed rats have shown that calcium antagonists more effectively antagonize vasopressor responses to exogenous noradrenaline (NA) than those to sympathetic nerve stimulation (Pedrinelli & Tarazi, 1984). However, in studies on perfused tissues, calcium antagonists seem to affect vasoconstrictor responses to NA and electrical nerve stimulation (ENS) to a similar degree Lippton et al, 1987;Kadowitz et al, 1988). In the rabbit isolated ear artery (REA), supplied with a dense adrenergic innervation, contractions elicited by ENS were even more sensitive to calcium antagonists than were those induced by NA (Kajiwara & Casteels, 1983).…”

A comparison of the effects of angiotensin II and Bay K 8644 on responses to noradrenaline mediated via postjunctional α1‐and α2‐adrenoceptors in rabbit isolated blood vessels

“…For example, All was found to potentiate responses to NA in a number of isolated vascular preparations such as perfused mesenteric arteries from a number of species (Malik & Nasjletti, 1976;Chiba & Tsukada, 1986; Panisset & Bourdois, 1968), human digital arteries (Moulds & Worland, 1980) and in canine hindpaw (Zimmerman & Kraft, 1979). It is noteworthy that a re-examination of the aadrenoceptor population in many of these preparations has revealed the presence of the a2-subtype as in human digital arteries (Glusa & Mardwardt, 1983;Stevens & Moulds, 1985); feline mesenteric vascular beds (Lippton et al, 1987) and canine saphenous artery (Sulpizio and Hieble, 1987).…”

“…For example, while Bay K 8644 can enhance postjunctional a2-adrenoceptor-mediated responses in a number of vascular preparations such as the rat saphenous vein (Cheung, 1985), feline mesenteric bed (Lippton et al, 1987) or canine saphenous artery (Sulpizio & Hieble, 1987), responses to NA, in the presence of prazosin (a2-adrenoceptor-mediated), are unaffected by Bay K 8644 in the human hand vein (Arner et al, 1988). In addition, postjunctional a,-adrenoceptor-mediated responses are facilitated by Bay K 8644 and reduced by nimodipine in human hand veins (Arner et al, 1988), but in contrast are resistant to the action of Bay K 8644 in the canine saphenous vein (Eskinder & Gross, 1987).…”