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Effects of icatibant on the ramipril-induced decreased in renal lithium clearance in the rat.
- Source :
-
Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2001 Mar; Vol. 363 (3), pp. 281-7. - Publication Year :
- 2001
-
Abstract
- The interaction between an inhibitor of angiotensin I converting enzyme (ramipril) and renal lithium handling was analysed in conscious, normotensive Wistar rats in the absence or the presence of a specific bradykinin B2 receptor antagonist, icatibant. The rats were treated for 5 days with ramipril (1 mg/kg/day p.o.) or its vehicle, alone or together with icatibant (0.1 mg/kg/day, s.c. infusion). Lithium chloride (8.3 mg/kg i.p.) was given as a single dose on day 5. Systolic blood pressure and heart rate were measured by tail plethysmography on day 3 (3, 9 and 15 h after ramipril administration) and renal function on day 4 (0-6 and 6-24 h urine sampling) and day 5 (0-6 h urine sampling). In another group of rats, 24 h sodium excretion was assessed during the first 4 days of ramipril treatment. Ramipril decreased renal lithium clearance (90+/-8 vs. 142+/-10 microl/min/100 g, P<0.001, n=24) and increased the fractional lithium reabsorption (74.3+/-1.9 vs. 66.7+/-1.7%, P<0.05) and plasma lithium concentration (0.108+/-0.006 vs. 0.085+/-0.004 mM, P<0.01). Alteration of renal lithium handling by ramipril was associated with a decrease in systolic blood pressure (-15% 3 h after ramipril administration) and sodium excretion (0-6 h after ramipril). The 24-h sodium excretion, however, tended to increase. Icatibant had no effect per se on renal function but attenuated the ramipril-induced decrease in renal lithium clearance (118+/-16 vs. 90+/-8 microl/min/100 g, n=12 and 24 respectively, P<0.05 one-tailed test) and systolic blood pressure. These results suggest that endogenous bradykinin contributes to the ramipril-associated alteration in renal lithium handling. Bradykinin B2 receptor-mediated vasodilation seems to be involved.
- Subjects :
- Animals
Blood Pressure drug effects
Bradykinin physiology
Depression, Chemical
Drug Interactions
Kidney metabolism
Lithium urine
Lithium Chloride administration & dosage
Lithium Chloride pharmacokinetics
Male
Rats
Rats, Wistar
Receptor, Bradykinin B2
Sodium metabolism
Sodium urine
Angiotensin-Converting Enzyme Inhibitors pharmacology
Bradykinin analogs & derivatives
Bradykinin pharmacology
Bradykinin Receptor Antagonists
Kidney drug effects
Lithium pharmacokinetics
Ramipril pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0028-1298
- Volume :
- 363
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Naunyn-Schmiedeberg's archives of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 11284442
- Full Text :
- https://doi.org/10.1007/s002100000353