Attenuated renal response to moxonidine and rilmenidine in one kidney‐one clip hypertensive rats

Abstract

1I, non-adrenoceptor, imidazoline receptor agonists, such as moxonidine, increase urine flow rate and sodium excretion following infusion into the renal artery. The functions of these agonists in genetic and acquired models of hypertension have not been determined. 2 We therefore studied the renal effects of two known non-adrenoceptor, imidazoline receptor agonists, rilmenidine and moxonidine, in 1K-IC hypertensive and 1K-sham normotensive rats. Rilmenidine (0, 3, 10, 30 nmol kg-' min-') or moxonidine (0, 1, 3, 10 nmol kg-' min-') was infused directly into the renal artery (30 gauge needle) of 1K-sham normotensive and 1K-IC hypertensive rats. 3 In 1K-sham normotensive rats, rilmenidine and moxonidine produced dose related increases in urine flow rate, sodium excretion and osmolar clearance. Both rilmenidine and moxonidine failed to increase urine flow rate, sodium excretion and osmolar clearance in 1K-IC hypertensive rats to the same extent as in 1K-sham animals. At comparable doses, rilmenidine had no effect, while moxonidine (3 and 10 nmol kg-' min-') did result in a small increase in urine volume and osmolar clearance which was less than that observed in the 1K sham control animals. 4 These studies indicate that the renal effects of non-adrenoceptor, imidazoline receptor stimulation are diminished in 1K-IC hypertensive rats compared with 1K-sham normotensive rats. Whether this decrease in activity of the natriuretic non-adrenoceptor, imidazoline receptors contributes to the increase in blood pressure in the 1K-IC acquired model of hypertension remains to be determined.

Influence of different dietary salts on the cardiovascular and renal effects of moxonidine in spontaneously hypertensive rats

“…However, the protective effect of moxonidine against proteinuria was lost during the high-sodium diet. Consistent with our finding, it has been shown previously that the renoprotective effect of moxonidine is also markedly attenuated in one kidney-one clip hypertensive rats, a model of salt-sensitive arterial hypertension (Li et al 1994).…”

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

“…It was found to be equally efficacious in elderly hypertensive patients [44] and those who also suffered from diabetes [45], renal impairment [46] or left ventricular hypertrophy [47]. In animal studies, rilmenidine has been shown to increase sodium excretion and urine flow rates [48]. It is comparable with atenolol [49] and hydrochlorothiazide [47] as a first line antihypertensive.…”

Imidazoline Receptors but Not α2-Adrenoceptors Are Regulated in Spontaneously Hypertensive Rat Heart by Chronic Moxonidine Treatment

“…Chronic treatment with the prototypic antidepressant imipramine, down-regulates I 1 -receptors in rat brainstem, without affecting ␣ 2 -adrenoceptors (Zhu et al, 1997). Also, renal I 1 -receptors are up-regulated by subpressor doses of angiotensin II infusion (Ernsberger et al, 1991), and in kidneys of SHR (El-Ayoubi et al, 2002b), whereas ␣ 2 -adrenoceptors are either unchanged or decreased in 1K1C rat kidneys (Li et al, 1994).…”