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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.

journal_name

Clin Exp Pharmacol Physiol

journal_title

Clinical and experimental pharmacology & physiology

authors

Jovanovska V,Eitle E,Harris PJ

doi

10.1111/j.1440-1681.2004.04008.x

keywords:

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

348-53

issue

5-6

eissn

0305-1870

issn

1440-1681

pii

CEP4008

journal_volume

pub_type

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Effects of rilmenidine on proximal tubular fluid absorption in rats.