Captopril given intracerebroventricularly, subcutaneously or by gavage inhibits angiotensin-converting enzyme activity in the rat brain

Evered, Mark; Robinson, Marilyn M.; Richardson, Mark A.

doi:10.1016/0014-2999(80)90419-7

Cited by 105 publications

(48 citation statements)

References 13 publications

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“…The doses of captopril used in this study were chosen on the basis of our previous finding that s.c. injections oflow doses block CE only in the circulation whereas higher doses block the synthesis of angiotensin II in the brain as well (Evered et al 1980). This differential effect of low and high doses was confirmed; the low dose of captopril (0)(1)(2)(3)(4)(5) (Printz et al 1982).…”

Section: Discussionmentioning

confidence: 99%

“…caused a small but significant decrease in drinking by water-deprived rats if given 45 or 60 min but not less than 30 min before water was returned. This does not reflect the time required for captopril to cross the blood-brain barrier since that seems to occur rapidly (Evered et al 1980). Further studies using chronic infusions of captopril i.c.v., rather than the S.C. approach used here, should help to identify the specific role ofa cerebral RAS.…”

Section: Enhancement Of Drinking By Captoprilmentioning

confidence: 94%

“…We believe that the dose of captopril was adequate to block angiotensin II synthesis because the pressor response to the same dose of renin was attenuated. The failure to reduce the thirst response could be explained if angiotensin I were as dipsogenic as angiotensin II, but it has been demonstrated that this is not the case, at least at the site of action of angiotensin peptides in the brain (Fitzsimons, Epstein & Johnson, M. D. EVERED AND M. M. ROBINSON 1978;Evered et al 1980;Mann, Schiller, Schiffrin, Boucher & Genest, 1981). Another possibility is that the conversion of angiotensin I to II occurs as readily in the brain of the captopril-treated rat (low dose) as it normally would in the pulmonary vasculature.…”

Section: Enhancement Of Drinking By Captoprilmentioning

confidence: 99%

“…injections of precursors of angiotensin II but not angiotensin II itself. Given subcutaneously in low doses it blocks CE only in the circulation; in high doses it prevents the synthesis of angiotensin II in both the circulation and the brain (Evered, Robinson & Richardson, 1980).…”

Section: Introductionmentioning

confidence: 99%

“…(angiotensin I and angiotensin II, 10 pmol; Peninsula Laboratories, Canada the circulation or in a higher dose (100 mg/kg) to block CE in the brain as well (Evered et al 1980). …”

Section: Introductionmentioning

confidence: 99%

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

Evered¹,

Robinson²

1984

The Journal of Physiology

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Enhancement Of Drinking By Captoprilmentioning

confidence: 94%

Section: Enhancement Of Drinking By Captoprilmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…(angiotensin I and angiotensin II, 10 pmol; Peninsula Laboratories, Canada the circulation or in a higher dose (100 mg/kg) to block CE in the brain as well (Evered et al 1980). …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Evered¹,

Robinson²

1984

The Journal of Physiology

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Angiotensin‐Converting Enzyme Inhibitors: Mechanistic Controversies

1989

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Many studies have investigated the mechanisms responsible for the therapeutic effects of the angiotensin converting enzyme inhibitors. Initially, the hemodynamic changes that occur with these agents were attributed solely to the inhibition of the renin-angiotensin-aldosterone system in plasma. Further research suggested other mechanisms were operable as a relationship was not always evident between hemodynamic changes and inhibition of the plasma renin-angiotensin-aldosterone system. A relationship between the pharmacodynamics of these agents and the inhibition of vascular and tissue renin-angiotensin systems, however, has been observed. Mechanisms less likely to contribute to the actions of the angiotensin converting enzyme inhibitors are increases in bradykinin and prostaglandin concentrations, or inhibition in the renin-angiotensin system within the central nervous system. Ancillary cardiovascular effects of angiotensin converting enzyme inhibitors offer possible new therapeutic gains. An understanding of these mechanistic controversies and newly-defined cardiovascular actions of angiotensin converting enzyme inhibitors are important to clinicians using these agents.

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Angiotensin‐converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6‐hydroxydopamine rat model of Parkinsonism

Lopez-Real

Rey

Soto‐Otero

et al. 2005

J of Neuroscience Research

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It is now established that the brain possesses a local renin-angiotensin system and that angiotensin II exerts multiple actions in the nervous system, including regulation of striatal dopamine release. Furthermore, angiotensin activates NADPH-dependent oxidases, which are a major source of superoxide, and angiotensin-converting enzyme inhibitors, commonly used in the treatment of hypertension and chronic heart failure, have shown antioxidant properties in several tissues. Oxidative stress is a key contributor to the pathogenesis and progression of Parkinson's disease. In the present study, we treated rats with intraventricular injections of the dopaminergic neurotoxin 6-hydroxydopamine and subcutaneous injections of the angiotensin-converting enzyme inhibitor Captopril to study the possible neuroprotective effect of the latter on the dopaminergic system and on 6-hydroxydopamine-induced oxidative stress. Rats treated with Captopril and 6-hydroxydopamine showed significantly less reduction in the number of dopaminergic neurons (i.e., immunoreactive to tyrosine hydroxylase) in the substantia nigra and in the density of striatal dopaminergic terminals than 6-hydroxydopamine-lesioned rats not treated with Captopril. In addition, Captopril reduced the levels of major oxidative stress indicators (i.e., lipid peroxidation and protein oxidation) in the ventral midbrain and the striatum of 6-hydroxydopamine-lesioned rats. Our results suggest that angiotensin-converting enzyme inhibitors may be useful for treatment of Parkinson's disease and that further investigation should focus on the neuroprotective capacity of these compounds.

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Captopril given intracerebroventricularly, subcutaneously or by gavage inhibits angiotensin-converting enzyme activity in the rat brain

Cited by 105 publications

References 13 publications

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

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

Angiotensin‐Converting Enzyme Inhibitors: Mechanistic Controversies

Angiotensin‐converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6‐hydroxydopamine rat model of Parkinsonism

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