Premium
EFFECTS OF RILMENIDINE ON PROXIMAL TUBULAR FLUID ABSORPTION IN RATS
Author(s) -
Jovanovska Valentina,
Eitle Eveline,
Harris Peter J
Publication year - 2004
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2004.04008.x
Subject(s) - rilmenidine , idazoxan , imidazoline receptor , chemistry , endocrinology , medicine , antagonist , receptor , pharmacology , prazosin , agonist , biochemistry
Summary 1. The antihypertensive agent rilmenidine has threefold higher affinity for I 1 imidazoline receptors compared with α 2 ‐adrenoceptors and acts on the central nervous system by reducing sympathetic activity and in the kidney by inhibiting Na + /H + exchange activity. 2. 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. 3. 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. 4. In the presence of the I 2 > I 1 /α 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 α 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 α 2 ‐adrenoceptors are involved in the luminal actions of rilmenidine. 5. The effects of luminal and peritubular administration of α‐methylnoradrenaline (an α 2 ‐adrenoceptor agonist) were compared with those of rilmenidine. Luminal α‐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 α‐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 α‐methylnoradrenaline indicate that both imidazoline receptors and α 2 ‐adrenoceptors are involved in the actions of these compounds on proximal fluid uptake.