Metoprine-induced thirst and diuresis in Wistar rats

In the present study, the renal responses to metoprine, a histamine-N-methy ltransferase inhibitor, were studied in conscious rats. Metoprine (10-20 mg kg(-1)) or vehicle were administered i.p, to male Wistar rats and the effe cts were followed for the subsequent 24 h. it was found that as early as 3 h after the drug administration metoprine 20 mg kg(-1) had increased water consumption and urine flow approximate to 6-8-fold. The treatment decreased urine osmolarity and increased free water clearance, but caused no change in plasma renin activity or plasma vasopressin concentration. In addition, a metoprine induced elevation in the systolic blood pressure was observed d uring the first few hours of the experiment. During the nocturnal period of the study, glomerular filtration rate and the excretion of electrolytes di d not increase in metoprine-treated rats as they Bid in control rats. A dec rease in the release of atrial natriuretic peptide was also found. The pres ent results show that inhibition of histamine catabolism by metoprine cause s massive changes in renal functions. It seems to promote water excretion b y the kidneys but, on the other hand, to reduce the excretion of electrolyt es. Although the exact mechanisms, especially the role of increased blood p ressure and nocturnal suppression of atrial natriuretic peptide, require fu rther clarification, the present data suggest that renin-angiotensin system and vasopressin were not involved in these renal responses to metoprine.