EFFECTS OF RENAL IMIDAZOLINE-RECEPTOR STIMULATION BY MOXONIDINE
Abdehamid M. Elhawary and Wael Hamdy Mansy*
Departments of Pharmacology & Therapeutics, Faculty of Medicine, Benha University and Faculty of Medicine, Cairo University*
Moxonidine is a centrally acting antihypertensive drug that induces its action through stimulation of imidazoline receptors in the rostral ventrolateral medulla. Stimulation of imidazoline receptors centrally, in addition to have a vasodepressor action, could also contribute to the regulation of water and solute excretion. Quantitative receptor autoradiography showed that I1 imidazoline sites are present in all regions of the kidney. Moxonidine shows almost identical affinity for I1-imidazoline binding sites in the rat renal medulla as in the bovine brainstem. It is not clear as to whether central and peripheral I1 imidazoline receptors function exclusively of each other to alter renal imidazoline receptor stimulation through intra-renal administration of moxonidine, in modulating renal hemodynamics and tubular excretion irrespective of changes in blood pressure or renal nerve activity. To avoid any systemic effects, moxonidine was injected into the renal artery through a fine catheter introduced retrogradely into the suprarenal artery. Then, the possible changes of mean arterial pressure (MAP), heart rate (HR), renal blood flow (RBF), renal arterial conductance, glomerular filtration rate (GFR), urine volume and urinary Na and K excretion were all detected after the injection of different doses of moxonidine. It was originally believed that the effects caused by moxonidine were partly a result of its action as an agonist at α2 adrenoceptors. Therefore the involvement of prostanoid in mediation of moxonidine actions was also investigated through determing its effects before and after pretreatment with the cyclo-oxygenase inhibitor indomethacin. Stimulation of imidazoline receptors in the kidney through intra-renal arterial administration of moxonidine in doses that did not alter MAP or HR induced renal vasodilatationand increment of RBF and GFR. Moxonidine induced significant diuretic, natriuretic but no kaliuretic effects. Moxonidine effects are not all mediated through α2 receptors but the hemodynamic effects may involve the release of vasodilator cyclo-oxygenase products.