title: Effects of rilmenidine on proximal tubular fluid absorption in rats.
abstract: The antihypertensive agent rilmenidine has threefold higher affinity for I(1) imidazoline receptors compared with alpha(2)-adrenoceptors and acts on the central nervous system by reducing sympathetic activity and in the kidney by inhibiting Na(+)/H(+) exchange activity. In the present study, we examined: (i) the effects of luminal and peritubular administration of rilmenidine on fluid absorption in superficial proximal tubules; and (ii) the nature of the receptors involved in mediating the action of this drug in the presence of specific antagonists (efaroxan, idazoxan and 2-methoxy-idazoxan). Studies were performed in anaesthetized Sprague-Dawley rats using shrinking split-drop micropuncture. Luminal administration of rilmenidine (10(-5) and 10(-13) mol/L) inhibited proximal tubular fluid absorption. Peritubular rilmenidine at 10(-12) and 10(-13) mol/L also inhibited fluid uptake, whereas rilmenidine at 10(-11) mol/L had a significant stimulatory action. In the presence of the I(2) > I(1)/alpha(2)-adrenoceptor antagonist idazoxan (10(-5) mol/L), luminal rilmenidine (10(-5) mol/L) stimulated fluid absorption. Stimulation of fluid uptake was also observed when rilmenidine (10(-5) mol/L) and the I(1) imidazoline receptor antagonist efaroxan (10(-5) mol/L) were added together in the luminal fluid. Luminal administration of the selective alpha(2)-adrenoceptor antagonist 2-methoxy-idazoxan (10(-5) mol/L) resulted in significant attenuation of the inhibitory action of luminal rilmenidine (10(-5) mol/L). This indicates that both I(1) imidazoline receptors and alpha(2)-adrenoceptors are involved in the luminal actions of rilmenidine. The effects of luminal and peritubular administration of alpha-methylnoradrenaline (an alpha(2)-adrenoceptor agonist) were compared with those of rilmenidine. Luminal alpha-methylnoradrenaline, at higher concentrations (10(-7) and 10(-5) mol/L), inhibited fluid absorption, as was seen with peritubular rilmenidine, but, in contrast with rilmenidine, no stimulatory action was observed. Peritubular alpha-methylnoradrenaline inhibited fluid uptake at higher concentrations (10(-5) and 10(-7) mol/L), whereas rilmenidine at these concentrations had no effect. The differences in the concentration-dependent responses for rilmenidine and alpha-methylnoradrenaline indicate that both imidazoline receptors and alpha(2)-adrenoceptors are involved in the actions of these compounds on proximal fluid uptake.
authors.affiliation: Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Jovanovska
authors.forename: Eveline
authors.initials: E
authors.lastname: Eitle
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Harris
mesh_terms: D000042:Absorption / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D054755:Imidazoline Receptors; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000819:agonists / Q000378:metabolism; D000077769:Rilmenidine
chemical_list: D054755:Imidazoline Receptors; D010080:Oxazoles; D011955:Receptors, Drug; D000077769:Rilmenidine