| Abstrakt: |
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 µl/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 µl/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. [ABSTRACT FROM AUTHOR] |
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