Tetrodotoxin-Insensitive Relaxation of Coronary Arterial Smooth Muscle to Electrical Stimulation: Possible Involvement of a Dopaminergic Mechanism

Abstract

Experiments were designed to determine the mechanism by which electrical stimulation causes tetrodotoxin-insensitive relaxation in isolated arteries. Rings of left anterior descending coronary arteries of dogs, pigs and calves were suspended in organ chambers between platinum electrodes. Experiments were performed after treatment with phenoxybenzamine and in the presence of propranolol. Calcium-free solution and calcium antagonists reduced the relaxation. Chemical denervation with 6-hydroxydopamine reduced the relaxation induced by electrical stimulation; in the presence of pargyline, the inhibitor of monoamine oxidase, it was virtually abolished. The nonselective dopaminergic antagonist droperidol and the selective DA₁-dopaminergic antagonist SKF R83566 caused a concentration-dependent inhibition of the relaxation; the DA₂-dopaminergic antagonist domperidone was ineffective. High concentrations of dopamine induced relaxation of the coronary smooth muscle; the relaxation was inhibited by SKF R83566 but not by droperidol. These results suggest that electrical stimulation causes relaxation by liberating an endogenous vasodilator substance, which acts on DA₁-dopaminergic receptors of the coronary smooth muscle.

Loss of contractile activity of endothelin‐1 induced by electrical field stimulation‐generated free radicals

“…Moreover, hydroxyl radicals generated by 0.1 mM H202 plus 0.2 mM FeSO4 (Fenton reaction, Freeman & Carpo, 1982) decreased ir-ET-1, and this decrease was significantly inhibited by 10-4 M deferoxamine, a ferrous chelator, and 1200 u ml-' catalase ( Figure 7). ET-1, and PGF2a which is frequently used for the investigation of EFS-induced relaxation of blood vessels (Rooke et al, 1982;Cohen et al, 1983;Feletou & Vanhoutte, 1989). After applying EFS to Krebs-Ringer solution containing each vasoconstrictor (1 tLM AVP, 1 pIm All and 2 !LM PGF2,), the contractile activity of each vasoconstrictor was investigated on porcine coronary artery strips for PGF2, and rat aorta strips for AVP and All.…”

“…To investigate whether prolonged EFS induces suppression of the contractile activity of other vasoactive agents or not, we studied the effect of EFS on the contractile activities of .the vasoactive agents, arginine'-vasopressin (AVP) and angiotensin-TI (All), since each is a peptide vasonconstrictor like ET-1, and PGF2a which is frequently used for the investigation of EFS-induced relaxation of blood vessels (Rooke et al, 1982;Cohen et al, 1983;Feletou & Vanhoutte, 1989).…”

“…Such relaxations are generally thought to be caused either by the activation of postjunctional P-adrenoceptors secondary to release of catecholamines from adrenergic nerve endings (Cohen et al, 1983) or by the release of vasorelaxant substances from noradrenergic and noncholinergic nerves (McCulloch & Edvinsson, 1980;Toda, 1982;Fujimori et al, 1989;Verma et al, 1993) or from the endothelium (Buga & Ignarro, 1992;Van Riper & Bevan, 1992). However, EFS-induced responses in isolated blood vessels show wide variation, depending on the segment of artery, species and stimulation conditions (Rooke et al, 1982;Feletou & Vanhoutte, 1989). Some investigators have recently demonstrated that the production of oxygen-derived free radicals by EFS could provoke vasodilator responses (Lamb & Webb, 1984;Greenberg et al, 1986).…”