Effects of methylglyoxal on adrenergic transmission in isolated rabbit intestine

The mechanisms for the toxic effects of the endogenous antiproliferative aldehyde methylglyoxal on the cardiovascular and central nervous systems are unclear. Possible interactions with adrenergic transmission were studied in the rabbit small intestine and rat aorta in vitro. Methylglyoxal had two opposing actions on the relaxant response to adrenaline and sympathetic nerve stimulation in the intestine. There was an increase in both responses in the presence of 10 mum-methylglyoxal, whereas 100 mum reduced them. The facilitation of adrenergic function was blocked by propranolol and mimicked when isoprenaline was used as the agonist. Methylglyoxal did not affect the baseline tension of the intestine or the aorta, nor did it affect noradrenaline-evoked contractions of the aorta. Similarly, concentrations of up to 1 mm-methylglyoxal did not affect active Na(+) transport, as assessed in isolated frog skin, or nerve impulse conduction, as determined in isolated frog sciatic nerve. It would appear that relatively low concentrations of methylglyoxal can selectively enhance beta-adrenoceptor- and inhibit alpha(2)-adrenoceptor-mediated responses.