inhibitory effects of melatonin on vascular reactivity: possible role of vasoactive mediators

The aim of this study was to investigate the effect of melatonin [MEL] on isolated rabbit aortic rings and its role in the vascular reactivity to contractile agents, noradrenaline [NA] and phenylephrine [PHE], as well as the relaxant agents [acetylcholine and sodium nitroprusside]. In addition, the levels of nitric oxide [NO], cyclic guanosine monophosphate [cGMP], total calcium, lipid peroxides, superoxide dismutase [SOD] and glutathione [GSH] were also investigated in the tissue homogenates of rabbit aortic rings pre-incubated [20 min] in MEL with and without contractile agents. The result revealed that MEL has an endothelium dependent vaso-relaxant effect and potentiated significantly the vaso-relaxant effect of acetylcholine. Moreover, MEL [10-4M] had a significant inhibitory effect on the contractile responses of aortic rings to both NA and PHE. In comparison with the control tissue rings, the levels of lipid peroxides were significantly increased; while those of GSH and SOD activities were significantly decreased in the tissue homogenates of aortic rings pre-incubated [20 min] in NA or PHE. In addition, the levels of NO and cGMP were significantly lower in the tissue rings pretreated with NA and PHE, respectively. The levels of total calcium were significantly increased in only tissue rings pretreated with NA. The levels of lipid peroxides were significantly decreased; while those of GSH, NO, cGMP and SOD activities were significantly increased in tissue homogenates of aortic rings incubated [20 min] in MEL [10-4 M] in comparison with ring tissues incubated in NA or PHE alone. In aortic rings incubated In MEL + PHE, the levels of lipid peroxides were significantly lower; while those of GSH, cGMP and SOD activities were significantly higher than their levels in ring tissues incubated in PHE. In aortic rings incubated in MEL + NA, the levels of lipid peroxides and total calcium were significantly lower; while those of NO were significantly higher than their levels in ring tissues incubated in NA alone

Sodium nitroprusside inhibits the intracellular calcium storage and release in rabbit aorta

This study aimed to investigate the possible involvement of the K+ channels by performing concentration response curves of SNP on K+Cl- precontracted aorta. The effect of SNP on the process of Ca2+ release from ic stores by studying its effect on phenylephrine induced contractions in Ca2+ free solution was also studied. The effect of SNP on the process of filling of the ic stores after their emptying by repeated application of phenylephrine in Ca2+ free solution and before the filling period in which the aorta was incubated in normal salt solution containing Ca2+ was evaluated. The possible involvement of endothelium in the SNP induced vasorelaxation was also investigated. The results showed that the relaxant effect of SNP is not endothelium dependent. SNP completely abolished contractions induced by low K+ and partially abolished contractions induced by high K+. SNP produced a significant dose dependent inhibition of the process of filling of the ic stores of Ca2+ and the process of Ca2+ release from these stores

Effects of lidocaine and verapamil on the reactivity of isolated rabbit aortic rings

The effects of lidocaine on the reactivity of isolated rabbit aortic rings to the contractile agents [norepinephrine and potassium chloride] as well as to both endothelium dependent [acetylcholine] and non endothelium dependent [sodium nitroprusside] vasodilators were investigated. Aortic rings were mounted for isometric tension recording. Cumulative dose response curves were constructed for these contractile and vasodilator agents in the presence of lidocaine or verapamil which was used for comparison and determination of the possible interaction of the two drugs when used together. Pretreatment with lidocaine [1 x 10 -4 M] for ten minutes significantly potentiated the contractile effect of high concentrations of norepinephrine and inhibited the contractile effect of potassium chloride. Lidocaine pretreatment produced significant inhibition of the relaxant effect of acetylcholine on the norepinephrine precontracted aortic rings. Verapamil [3 x 10 -6 M] pretreatment for ten minutes produced significant inhibition of the contractile effect of KCl. Verapamil produced insignificant inhibition of the relaxant effect of acetylcholine, but potentiated the inhibitory effect of lidocaine. Both lidocaine and verapamil produced insignificant inhibition of the relaxant effect of sodium nitroprusside, but when used together, they reduced the sensitivity to sodium nitroprusside. The results indicated that the calcium antagonistic property of lidocaine may be lined to other mechanisms in addition to its sodium channel blocking activity