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PubMed1975

Xipamid, a potent new diuretic.

The effects of xipamid and frusemide were comapred in 9 oedematous patients. Xipamid was found to be equipotent with frusemide in doses of 40 mg. and 80 mg., with respect to its effect on sodium and water excretion. The time course of action of xipamid was observed to be more prolonged than that of frusemide. It is concluded that xipamid is a potent and safe diuretic.

Adult↗
PubMed2001

Insulin resistance induced by loop diuretics and hyperosmolarity in perfused rat liver.

Insulin-induced cell swelling was recently suggested to reflect an independent signal for metabolic insulin effects such as inhibition of hepatic proteolysis, which is transmitted at the level of autophagosome formation via p38MAPK activation [Häussinger et al., Gastroenterology 116 (1999), 921-935]. Here, the role of insulin-induced cell swelling in the overall context of insulin signalling towards proteolysis inhibition was studied in perfused rat liver. Loop diuretics and hyperosmolarity, which impair insulin-stimulated cell swelling, strongly blunt Erk-2 and p38MAPK activation as well as proteolysis inhibition by insulin, but are without effect on insulin-induced tyrosine phosphorylation of IR-beta and IRS-1. Inhibitors of phosphatidylinositol-3-kinase (PI3-kinase) also block insulin-induced cell swelling, MAP kinase activation and proteolysis inhibition, but the antiproteolytic response to hypoosmolarity remains unaffected. We suggest that PI3-kinase-mediated cell swelling induced by insulin is required to amplify the insulin signal to MAP kinases and thus proteolysis regulation. The perturbation of insulin-induced cell swelling may be of pathophysiological relevance for the development of insulin resistance in clinical situations associated with hyperosmotic dehydration and loop diuretic treatment.

Animals↗
PubMed1978

Inhibitory effect of 1,4-dimorpholino-7-phenylpyrido[3,4-d]-pyridazine (DS-511) and its 4'-hydroxy derivative on antidiuretic action of vasopressin in rats.

The water-diuretic features of 1,4-dimorpholino-7-phenylpyridol[3,4-d]-pyridazine (DS-511) and its water-soluble 4'-OH derivative [DS-511(4'-OH)] were investigated. In saline-infused rats the minimum i.v. diuretic dose of DS-511(4'-OH) was 1.0 micrograms/kg/min, while in water-diuretic rats the minimum dose was 50 micrograms/kg/min. Intravenous infusion of DS-511 or DS-511(4'-OH) at rates of 1 to 10 micrograms/kg/min caused a dose-dependent inhibition of the ADH-induced antidiuresis in water-diuretic rats, and a decrease in urinary osmolality. However, hydrochlorothiazide even at 500 micrograms/kg/min did not alter the antidiuresis, but increased the osmolality. Furosemide at a rate of 10 micrograms/kg/min increased urinary excretion of water and sodium in both saline-infused and water-diuretic rats, but the same dose did not inhibit the ADH-induced antidiuresis. These findings indicate that the specific anti-ADH action at relatively low doses of DS-511 and DS-511(4'-OH) is partly involved in the diuretic mechanism of these agents.

Animals↗