EFFECT OF MOXONIDINE ON URINARY ELECTROLYTE EXCRETION AND RENAL HEMODYNAMICS IN MAN

Moxonidine and related compounds have been recently introduced into antihypertensive therapy. It is thought that these drugs exert their blood pressure lowering effect through interaction with nonadrenergic receptors in the central nervous system, i.e. imidazoline receptors, although the contribution of specific interaction with al-receptors is still under debate. Imidazoline receptors have recently been documented in the renal proximal tubule. In experimental studies, interaction of imidazolines with these receptors decreased the activity of the Na+/H+ antiporter and induced natriuresis. To quantitate the effect of the imidazoline receptor agonist moxonidine on renal sodium handling and renal haemodynamics in man, we examined ten healthy normotensive males (aged 25 +/- 4 years) in a double blind placebo-controlled study using a crossover design. Subjects were studied on a standardized salt intake (50 mmol per day). On the 7th and 10th study day they were randomly allocated to receive either i.v. placebo or i.v. 0.2 mg moxonidine. Urinary electrolyte excretion, lithium clearance (as an index of proximal tubular sodium handling), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), renal vascular resistance (RVR), mean arterial blood pressure (MAP), plasma renin activity (PRA) and plasma noradrenaline (NA) levels were assessed. Injection of moxonidine did not increase fractional sodium excretion or lithium clearance. Specifically, antinatriuresis was not observed after injection of moxonidine despite a significant decrease in MAP from 91 to 85 mmHg and a significant increase in PRA. MAP and PRA did not change with administration of placebo. Injection of moxonidine did not affect GFR and RVR; ERPF decreased slightly but not significantly. Acute administration of 0.2 mg i.v. moxonidine decreased blood pressure in healthy volunteers on standardized salt intake, but did not affect natriuresis, proximal tubular sodium reabsorption or glomerular filtration rate. The absence of an antinatriuretic response despite a decrease in blood pressure suggests a direct facilitation of natriuresis by moxonidine.