Marsanidine and 7-Me-marsanidine, the new hypotensive imidazolines augment sodium and urine excretion in rats

BackgroundWe have recently described the synthesis and circulatory properties of two novel centrally acting imidazoline agents: marsanidine (1-[(imidazolidin-2-yl)imino]indazole) and 7-Me-marsanidine (1-[(imidazolidin-2-yl)imino]-7-methylindazole). Marsanidine has proven to be a highly selective α2-adrenoceptor ligand with the α2/I1 selectivity ratio of 3879, while 7-Me-marsanidine has been shown to be a mixed α2-adrenoceptor/imidazoline I1 receptor agonist with the α2/I1 selectivity ratio of 7.2. In the same paper, we indicated that iv administration of both compounds toWistar rats induced a decrease in blood pressure and heart rate. The hypotensive effect of the iv administered imidazolines might be mediated not only through activation of the central α2 and/or I1 receptors but also through subsequent decrease of the renal sympathetic nerve activity and a direct effect on peripheral receptors. The present studies were performed to determine whether the newly synthesized compounds might influence the diuresis and sodium excretion in rats.MethodsBoth compounds were infused iv to anesthetized rats in the dose of 100 μg/kg b.w. The diuresis and sodium concentration in urine and blood samples were determined. The mean arterial blood pressure and heart rate were monitored directly throughout the experiment.ResultsAsignificant increase of diuresis and natriuresis was observed within 40 min after the administration of both marsanidine and 7-Me-marsanidine, in comparison to both the control period and the control group. However, between the 20 and 40 min of the experiment the natriuretic and diuretic effect of 7-Me-marsanidine was markedly higher than that of marsanidine.ConclusionOur study indicates that the new hypotensive imidazoline compounds of marsanidine and 7-Me-marsanidine increase diuresis and natriuresis in rats. However, the effect of 7-Me-marsanidine is markedly more potent, probably due to its moderate affinity to the I1-imidazoline receptor.