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Apparent Absence of Direct Renal Effect of Imidazoline Receptor Agonists

Abstract: Imidazoline receptor agonists such as moxonidine and rilmenidine increase sodium excretion whether administered within the central nervous system, intravenously, or directly into the renal artery. To determine if this natriuresis was mediated by a direct renal effect and was independent of the renal sympathetic nerves, we used two different preparations in the pentobarbital‐anesthetized rat. In the first series of studies, rats were unilaterally nephrectomized 7 to 10 days before the experiment. On the day of the experiment, the remaining kidney was denervated (surgical and 10% phenol/ 95% ethyl alcohol) or sham treated. The effect of an intravenous infusion of rilmenidine was determined. Rilmenidine (10 nmol/kg/minute) decreased blood pressure and increased urine flow rate and sodium excretion in the sham‐ but not the denervation‐treated rats. The response to furosemide (5.05 nmol/kg/minute) remained intact following denervation. We then used a two‐kidney rat model that allowed for separate urine collection from each ureter. We used low infusion rates of moxonidine directly into the left renal artery. An increase in urine flow rate from the left but not the right kidney would suggest a direct renal action. Low infusion rates of moxonidine (10, 30 nmol/kg/minute) increased urine flow rate similarly from both ureters. A low infusion rate of furosemide (9.1 nmol/kg/minute) into the left renal artery increased urine flow rate only from the left ureter. The failure of moxonidine to increase urine flow rate selectively only in the left kidney indicated the agonist acts at an extrarenal site to increase urine flow rate from both kidneys equally. The complete attenuation of the response to rilmenidine indicates the importance of the renal nerves and suggests that the extrarenal site is most probably the central nervous system. Collectively, these studies do not support a direct renal action of imidazoline agonists in producing natriuresis.