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

Background:we 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 a2-adrenoceptor ligand with the a2/i1 selectivity ratio of 3879,while 7-me-marsanidine has been shown to be a mixed a2-adrenoceptor/imidazoline i1 receptor agonist with the a2/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 ?2 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. methods: both compounds were infused iv to anesthetized rats in the dose of 100 ?g/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. results: asignificant 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. conclusion: our 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.