The effect of vasodilator drugs on the noradrenaline constrictor response in the isolated mesenteric artery

Abstract

1969. The effect of vasodilator drugs on the noradrenaline constrictor response in the isolated mesenteric artery. Can. J. Physiol. Pharmacol. 47,[663][664][665][666][667][668][669] Previous reports have indicated that diazoxide will inhibit the vasoconstrictor response to noradrenaaine on isolated aortic strips (Wohl et al. Life Sci-7,381 (1968)). Inhibition of the noradrenaaine response was dependent on the calcium concentrations. The present study has confirmed this observation in an isolated perfused rnesenteric artery preparation. In addition, a calcium-dependent inhibition of the raoradrena8ine constrictor response was found with theophylline and sodiuna nitrite but isoproterenol did not inhibit the noradrenaline response. It is suggested that the drugs which inhibit noradrenaline rnay do so by either blocking calcium receptors or by depleting an intracellular calcium pool necessary for drug-induced vasoconstriction; or by preventing calcium release from such a pool. Blockade of alpha adrenergic receptors is probably not involved since the drugs also blocked the constrictor response to vasopressin. The mecha~aisrn of the inhibitory action of these drugs is probably not related to their effects on cyclic AMP.The methylated xanthine theophylline is known to produce a number of effects which are qualitatively similar to the beta effects of the adrenergic amines. For example, both groups of drugs can produce positive inotropic and chronotropic effects and vasodilation. In addition, both methylated xanthines and catecholamines can increase tissue levels of adenosine-3',5~-monophosphate (cyclic AMP), a nucleotide postulated to act as a second messenger mediating a variety of hormonal effects (Sutherland et al. 1968). Theophylline can increase the amount of cyclic AMP by inhibiting phosphodiesterase, the enzyme responsible for metabolism of the nucleotide (Butcher and Sutherland B 962) whereas catechollarnincs increase the amount of cyclic AMP by increasing the synthesis of the compound (see Sutherland et al. 1968). If both groups of drugs produce their cffects by increasing cyclic AMP levels, one by increasing synthesis and the other by decreasing the destruction of the nucleotide, it should be possible to enhance the effects of the catecholamines by pretreating the animal or isoBated tissue with theophylline. This has been shown to be the case in a number of studies.Theophylline will enhance the inotropic effect of adrenaline on isolated atrial strips (Rall and West 1 963 ) and the phosghorylase-activating effect of adrenaline in the isolated rat heart (Mess et al. 1963). These results support the hypothesis that cyclic AMP may be involved in the effects of both the catecholamines and theophylline. A more recent study (McNeill et al. 1969) demonstrated that potentiation by theophylline of the catecholamine--induced phosghorylase activation was not dose-related to the positive inotropic effect of theophylline and was probably better correlated with the effect of theophylline on the movement of calcium. The lite...

Actions of quazodine (MJ1988) on smooth muscle

“…Indeed, synergism between theophylline and quazodine was evident in the rabbit duodenum. Other experiments demonstrating similar actions of theophylline have been described by Northover (1968), McNeill, Barnes, Davis & Hook (1969), Wilkenfeld & Levy (1969) and Bowman & Hall (1970). 9 Many of the effects of isoprenaline and of theophylline are mediated by increased cellular concentrations of cyclic adenosine-3',5'-monophosphate (cyclic AMP) (Sutherland, Robison & Butcher, 1969;Butcher & Sutherland, 1962;Robison, Butcher & Sutherland, 1967;Turtle, Littleton & Kipnis, 1967).…”

Effects of Vasoactive Agents and Diuretics on Isolated Superfused Interlobar Renal Arteries

“…The highest doses of norepinephrine used (0.4 and 1 pg) were not antagonized significantly suggesting a competitive depression of reactivity. Thiazides have been reported to reduce vascular reactivity in other preparations (13)(14)(15)(16)(17). In this respect, this preparations appears to be similar to other vascular beds.…”

Effect of (±) dihydroxy ephedrine and (±) dihydroxy pseudoephedrine on adrenergic transmission in mesenteric arteries

“…The interpretation was strengthened by the abolition of these actions of isoprenaline by a B-receptor blocking agent, propranolol. In contrast, Rogers, Atkinson &Long (1966), andMcNeill, Barnes, Davis &Hook (1969) could obtain no evidence for the presence of fl-receptors in perfused mesenteric vessels of the dog.…”