Metoprine-induced thirst and diuresis in Wistar rats.
In the present study, the renal responses to metoprine, a histamine-N-methyltransferase inhibitor, were studied in conscious rats. Metoprine (10-20 mg kg(-1)) or vehicle were administered i.p. to male Wistar rats and the effects 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 approximately 6-8-fold. The treatment decreased urine osmolality 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 during the first few hours of the experiment. During the nocturnal period of the study, glomerular filtration rate and the excretion of electrolytes did not increase in metoprine-treated rats as they did in control rats. A decrease in the release of atrial natriuretic peptide was also found. The present results show that inhibition of histamine catabolism by metoprine causes massive changes in renal functions. It seems to promote water excretion by the kidneys but, on the other hand, to reduce the excretion of electrolytes. Although the exact mechanisms, especially the role of increased blood pressure and nocturnal suppression of atrial natriuretic peptide, require further clarification, the present data suggest that renin-angiotensin system and vasopressin were not involved in these renal responses to metoprine.
Lecklin
A
A
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
Eriksson
L
L
Leppäluoto
J
J
Tarhanen
J
J
Tuomisto
L
L
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006637:Histamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D011739:Pyrimethamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013894:Thirst / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D001127:Arginine Vasopressin; C006308:metoprine; D009320:Atrial Natriuretic Factor; D006637:Histamine N-Methyltransferase; D011739:Pyrimethamine