Site of action of moxonidine in the rat nephron

Moxonidine is a centrally acting antihypertensive agent which has been foun d to exert its blood pressure lowering effect by interaction with (alpha (2 )-adrenoceptors and imidazoline receptors of the I-1-type. These receptors have also been demonstrated to be present in the rat kidney. In the present study, clearance and micropuncture techniques were applied to anaesthetize d rats to localize the site of action of moxonidine within the nephron. The clearance data show that moxonidine (0.25 mg/kg i.v., followed by a contin uous i.v. infusion of 0.25 mg/h) induced a marked increase in urine flow an d urinary excretion of sodium, chloride and potassium. The changes in urine flow and urinary solute excretion were accompanied by an enhanced glomerul ar filtration rate. The micropuncture experiments revealed that moxonidine significantly increased glomerular filtration rate of superficial nephrons, and significantly inhibited fractional reabsorption of fluid, sodium, pota ssium and chloride by similar amounts (by 9.0%-9.8%) in superficial proxima l tubules. Regarding fluid and sodium reabsorption, the proximal effect of moxonidine was continuously weakened by a compensatory increase of reabsorp tion in the loop of Henle and the subsequent distal nephron segments. The i nhibitory effect of moxonidine on fractional proximal potassium reabsorptio n was completely compensated in the loop of Henle, but the drug induced a n et secretion of potassium into the segments lying beyond the early distal t ubule, probably as a consequence of the increased tubule fluid and sodium l oad delivered to them. The experiments have identified the proximal tubule as the principal nephron site where the diuretic action of moxonidine arise s. The proximal effect may be related to the increased glomerular filtratio n rate and to a direct inhibitory interaction of moxonidine with the proxim al Na+/H+ exchanger.