Increased or decreased thirst caused by inhibition of angiotensin‐converting enzyme in the rat.

Abstract

SUMMARY1. We have investigated the effects on water intake of subcutaneous (s.c.) injections of low (0 5 mg/kg) and high (100 mg/kg) doses of captopril, an inhibitor of angiotensin-converting enzyme (CE). Low doses block the synthesis of angiotensin II only in the circulation whereas high doses block CE in both the blood and the brain.2. The low dose of captopril enhanced drinking in response to three hypotensive drugs, isoprenaline (0-1 mg/kg, s.c.), phentolamine (5 mg/kg, s.c.) and serotonin (2 mg/kg, s.c.), whereas the high dose of captopril abolished drinking in response to these stimuli.3. The low dose of captopril also enhanced drinking in response to histamine (0-25-50 mg/kg, intraperitoneal, i.P.), but in this case the high dose of captopril only partially reduced the drinking response.4. The low dose of captopril enhanced drinking after 24 h water deprivation but high doses had no significant effect on deprivation-induced thirst.

Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

“…Recapitulating the overall Pattern Ranking graphics, liver toxicities are seen only at the low dose (Table 4). Such a paradoxical dose response has been seen for other effects of captopril, namely, the effect of this drug on drinking [38, 39], where captopril enhanced drinking at low doses but inhibited it at high doses. It is impossible to speculate if these diverse results are related.…”

Influence of Salt Intake, ANG II Synthesis and SFO Lesion on Thirst and Blood Pressure During Sodium Depletion

“…The effects of a low dose of a kininase II inhibitor, such as captopril, on water and saline intake have been well documented (Evered & Robinson, 1984;Fitts & Masson, 1990;Fitzsimons & Elfont, 1982;Lehr et al, 1973;Moe et al, 1984;Thunhorst et al, 1987;Weisinger et al, 1988). This low dose of captopril inhibits kininase II activity peripherally, and its administration results in increased circulating ANG I available to the forebrain circumventricular organs, including the SFO and the organum vasculosum of the lamina terminalis (OVLT) (Evered & Robinson, 1984;Fitts & Masson, 1990;Fitzsimons & Elfont, 1982;Thunhorst et al, 1987).…”

“…This low dose of captopril inhibits kininase II activity peripherally, and its administration results in increased circulating ANG I available to the forebrain circumventricular organs, including the SFO and the organum vasculosum of the lamina terminalis (OVLT) (Evered & Robinson, 1984;Fitts & Masson, 1990;Fitzsimons & Elfont, 1982;Thunhorst et al, 1987). These regions of the brain possess high concentrations of angiotensin converting enzyme, and, with increased ANG I available to these nuclei, a low dose of captopril has the effect of greatly enhancing local ANG II synthesis and drinking.…”

“…The high dose was expected to reduce water and saline intakes as in Experiment 1A, but the low dose was expected to greatly increase water and saline intakes (Evered & Robinson, 1984;Fitts & Masson, 1990;Fitzsimons & Elfont, 1982;Lehr et al, 1973;Moe et al, 1984;Thunhorst et al, 1987;Weisinger et al, 1988). If changes in water and saline intakes after the high dose of captopril in Experiment 1 were derived from greatly reduced MAP or from uremia resulting from anuria, then large differences in MAP and BUN correlated with the large differences in fluid intake should be observed.…”

Effects of lignans extracted from Eucommia ulmoides and aldose reductase inhibitor epalrestat on hypertensive vascular remodeling

“…Sex-, age-, and number-matched SHR and WKY were treated with drugs or same volume of distilled water as controls. Doses of captopril and epalrestat were administratered based on the literatures (Evered and Robinson, 1984;Inaba et al, 1999), while the dose of lignans was determined according to our previous studies (Luo et al, 2010). Twelve rats were used for each experimental group.…”