Effects of Hoe 065, a compound structurally related to inhibitors of angiotensin converting enzyme, on acetylcholine metabolism in rat brain

Wiemer, Gabriele; Becker, R. H. A.; Gerhards, Hermann J.; Hock, Franz J.; Stechl, Jens; Rüger, Wolfgang

doi:10.1016/0014-2999(89)90680-8

Cited by 14 publications

(3 citation statements)

References 28 publications

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“…context, Wiemer et al 20 have demonstrated that Hoe 065, a compound structurally related to ACE inhibitors, increases cholinergic activity within a physiological range through an enhancement of the release of acetylcholine. In the present study, we did not investigate the effects of the angiotensin inhibition on cholinergic activity in DS.…”

Section: Parameters Indicating Renal Functionmentioning

confidence: 99%

Long-Term Inhibition of Renin-Angiotensin System Sustains Memory Function in Aged Dahl Rats

Hirawa¹,

Uehara²,

Kawabata³

et al. 1999

Hypertension

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Abstract-The Dahl salt-sensitive (DS) rat, a genetic model of salt-induced hypertension in humans, is more likely to develop severe vascular injuries than a rat with spontaneous hypertension. We designed an experiment to scrutinize the effects of renin-angiotensin inhibition on cognitive dysfunction in the aged, normotensive DS with a passive avoidance test. Eighteen months of treatment with a very low dose of the angiotensin-converting enzyme (ACE) inhibitor cilazapril (2.5 g/mL in drinking water) or the angiotensin II type 1 receptor antagonist E4177 did not reduce blood pressure throughout the experiment, although in the low dose cilazapril group (12.5 g/mL in drinking water), blood pressure dropped within 6 months after treatment began. The cilazapril treatments dose-dependently improved memory function in the aged, normotensive DS fed a low-salt diet compared with the untreated, control rats. This improvement was associated with significant increases in hippocampal CA1 cells and capillary densities in the CA1 regions compared with those in the untreated DS. Similarly, E4177 slightly improved the memory dysfunction observed in the aged DS. The cells in the hippocampal CA1 region were restored slightly, but the capillary densities were not influenced by the receptor antagonist. On the other hand, the ACE inhibitor and receptor antagonist both attenuated urinary protein excretions with an improvement of glomerular sclerosis. These data suggest that long-term treatment with an ACE inhibitor improves memory dysfunction probably through restoration of capillary and hippocampal cells. The effects are due to the inhibition of the angiotensin II type 1 receptor and probably to the enhancement of the kallikrein-kinin system. (Hypertension. 1999;34:496-502.)Key Words: cilazapril Ⅲ angiotensin-converting enzyme inhibitors Ⅲ receptors, angiotensin Ⅲ memory Ⅲ cognition Ⅲ rats, aging Ⅲ aging R ecent advances in vascular physiology have emphasized an integration of multiple risk factors that form vascular lesions in patients with various disorders that affect the cardiovascular system. The understanding of the process of vascular lesion development has led to the establishment of pharmacological and nonpharmacological strategies for the prevention of vascular damage in hypertension, hyperlipidemia, or abnormal glucose metabolism. In addition to such acquired forms of risk factors, some inevitable factors, eg, gender, genetic loading, and aging, contribute to the progression of vascular injuries. Among these factors, aging is particularly important. The development of a therapeutic strategy for the aging population is urgently needed. In Japan, by year 2015, people Ն65 years of age will constitute 25% of the population, and worldwide, by year 2025, this population will have doubled. In addition, Ϸ50% of dementia or cognitive dysfunction in the elderly are attributable to cerebrovascular lesions. 1 The elucidation of the mechanism of cerebrovascular lesions related to the process of aging provides a useful strategy to preven...

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Section: Parameters Indicating Renal Functionmentioning

confidence: 99%

Long-Term Inhibition of Renin-Angiotensin System Sustains Memory Function in Aged Dahl Rats

Hirawa¹,

Uehara²,

Kawabata³

et al. 1999

Hypertension

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“…Another feasible mechanism is the interaction of RAoctil with the cholinergic system of the basal forebrain, since it was shown that IP administered RA-octil increased cholinergic activity in striatal areas in the same dose range where behavioral effects occurred (Wiemer et al 1989a). This interaction can also be proposed for the mnemogenic effect of SP in the basal forebrain, since this region contains a dense network of SP-immunoreactive fibers and terminals which make synaptic contact with cholinergic neurons (Bolam et al 1986;Beach et al 1987).…”

Section: Discussionmentioning

confidence: 98%

Mnemogenic effects of injecting RA-octil, a CE-inhibitor derivate, systemically or into the basal forebrain

Gerhardt

Hasenöhrl

Hock³

et al. 1993

Psychopharmacology

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The aim of this study was to investigate the effects of systemically or intracerebrally administered RA-octil, a derivative of the angiotensin converting enzyme (CE)-inhibitor ramipril, on memory and reinforcement and to compare its effectiveness with that of the neurokinin substance P (SP). In the first experiment systemic post-trial application of RA-octil and SP in the rat enhanced habituation, a learning task which does not require motivational treatments. Unlike SP, injection of RA-octil did not have reinforcing effects as measured with a conditioned place preference task. In the second experiment, a facilitation of inhibitory avoidance learning was obtained by injection of RA-octil or SP unilaterally into the basal forebrain immediately after the learning trial. In contrast, a 5 h delayed injection of RA-octil had no effects on learning. The results demonstrate memory-enhancing effects of RA-octil after systemic application as well as after injection into the basal forebrain. Furthermore, the mnemogenic effects of SP after central and peripheral administration were confirmed. Since RA-octil, although being structurally closely related to CE-inhibitors, does not affect plasma CE, yet exhibits mnemogenic effects, it is possible that "cognition-enhancing" actions of CE-inhibitors are dissociable from their action within the renin-angiotensin system.

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“…Secondly, Gerhards et al (1988) examined the effects of several ACE inhibitors on cognition in mice and found that their anti-amnestic properties did not correlate with their ability to block central ACE. Thirdly, Hoe 065, a compound that is structurally related to ACE inhibitors but that does not inhibit ACE, also produces effects on memory and learning tasks in rodents (Hock, Stechl and Rieger, 1989) and appears to increase brain cholinergic activity (Wiemer et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

The effects of pre-treatment with enalapril maleate on scopolamine-induced cognitive deficits in healthy volunteers

et al. 1991

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Two studies were undertaken to investigate the effects of acute (Study 1) or repeated (Study 2) administration of the angiotensin converting enzyme (ACE) inhibitor enalapril on the cognitive deficits produced by scopolamine administration in volunteers. Enalapril at doses between 2.5 and 10.0 mg p.o. produced virtually complete blockade of plasma ACE activity. However, it did not influence the effects of scopolamine on a variety of cognitive tasks, including tests of memory, attention and sedation.

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Effects of Hoe 065, a compound structurally related to inhibitors of angiotensin converting enzyme, on acetylcholine metabolism in rat brain

Cited by 14 publications

References 28 publications

Long-Term Inhibition of Renin-Angiotensin System Sustains Memory Function in Aged Dahl Rats

Long-Term Inhibition of Renin-Angiotensin System Sustains Memory Function in Aged Dahl Rats

Mnemogenic effects of injecting RA-octil, a CE-inhibitor derivate, systemically or into the basal forebrain

The effects of pre-treatment with enalapril maleate on scopolamine-induced cognitive deficits in healthy volunteers

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