A comparison of the natriuretic/diuretic effects of rat vs. human leptin in the rat

Intrarenal artery infusions of low-dose human, but not mouse, leptin cause diuresis/natriuresis in rats [E. K. Jackson and P. Li. Am. J. Physiol. 272 (Renal Physiol. 41). F333-F338, 1997]. The lack of effect of mouse leptin i n the rat could tee due to slight differences in the primary structure of m ouse vs. rat leptin, To test this hypothesis, we infused single doses of ra t (0.1, 0.3, 1, or 3 mu g/min) or human (3 mu g/min) leptin into the renal artery of rats for 140 min while continuously measuring blood pressure and the renal excretion rate of urine and electrolytes. Intrarenal infusions of rat leptin did not alter any measured parameter. Human leptin caused a del ayed diuresis/natriuresis (P < 0.0006 and P < 0.0049, respectively) that re quired similar to 2 h to achieve a maximum effect and that was not accompan ied by changes in blood pressure or potassium excretion. We conclude that l ow-dose human, but not low-dose rodent, leptin has direct diuretic/natriure tic activity. Our results can be explained from an evolutionary perspective , since obesity-induced hypertension would be a much greater selective forc e in hominids compared with rodents.