1. Saliva obtained from the parotid duct of normal and uraemic subjects had an average urea concentration of 86% of the plasma concentration whereas in mixed saliva obtained from the mouth the urea concentration was only 31% of the plasma concentration. Ammonia concentrations were low or unmeasurable in parotid saliva but varied between 0.6 and 26 mmol/kg in oral saliva, showing a positive correlation with the plasma urea concentration.2. The urea in samples of mixed oral saliva incubated at 37°C disappeared by 290 min. Ammonia steadily increased during incubation; within the first 100 min, the increase could be largely accounted for by bacterial hydrolysis of urea, but later non-urea sources became relatively more important.3. These findings suggest that the ammonia in mixed oral saliva is derived by bacterial hydrolysis of urea within the mouth. However, the concentration of ammonia plus urea nitrogen in oral saliva was only 76% of the urea nitrogen concentration of parotid saliva, which suggests that some ammonia is lost from the mouth by buccal absorption or by volatilization. 4.To assess the role of non-ionic diffusion of ammonia through the buccal mucosa, we studied the effect of pH on the disappearance of ammonia from buffered solutions retained in the mouth. Ammonia concentrations fell more rapidly at pH 9 than at pH 7, as also did those of hydrazine, a non-volatile analogue of ammonia which is known to be absorbed through other mucosae by non-ionic diffusion. These findings suggest that salivary ammonia is reabsorbed passively through the oral mucosa in the un-ionized phase.

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Metolazone, a new diuretic/saluretic/anti-hypertensive agent related to quinethazone, was used to treat 20 patients with impaired renal function. Among eight water loaded hospitalized patients given metolazone 5 mg intra venously, glomerular filtration rate rose in four and diminished slightly in four while urine flow and sodium excretion in creased significantly. In 12 out-patients given long-term oral metolazone (usually 5–10 mg in single daily doses) treatment effectively removed oedema and induced weight loss; in the seven initially hypertensive patients blood pressure decreased also. Plasma renin activity was measured in seven patients before and after several weeks’ metolazone therapy. Activity fell in two patients and rose in five, but the upper limit of normal was exceeded in one only. Renal epithelial cell excretion rates indicated that drug nephrotoxicity was absent. Mean creatinine clearances rose, serum potassium levels fell, and ten patients received oral potassium supplements. Small transient increases in liver enzymes were seen in three patients. Metolazone tended to maintain glomerular filtration rate and renal plasma flow while increasing salt and water losses. A proximal as well as a distal site of action was suggested for the drug, and its anti-hypertensive effect was confirmed.

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El prazosin fue usado en asociación con otros agentes antihipertensores convencionales, en 13 pacientes hipertensos adultos, de ambos sexos. La población estudiada incluyó 6 pacientes (46%) con hipertensión asociada a enfermedades nefropáticas, siendo 4 casos moderados (31%), 4 casos graves (31%) y 5 casos de evolución maligna (38%). Después de 5 meses de evolu-ción, se observe reducción significativa de los niveles de presión arterial supina (disminución media de 31/27 mm Hg) en todos los casos, con dosis diaria final de prazosin de 0.5 mg. Por otro lado, 4 pacientes (31%) tuvieron su presión arterial supina normalizada, mientras que 4 (31%) quedaron en el grupo leve, 3 (22%) en el moderado, 1 (8%) en el grave y 1 (8%) en el de evolución maligna. El plan terapéutico utilizado fue bien tolerado por los pacientes.