Disease relevance of Ace

• On the basis of evidence suggesting the activation of the kallikrein-kinin system in steroid-induced hypertension, we considered the possibility that the angiotensin-converting enzyme inhibitor captopril would lower the arterial blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats through kininase II inhibition [1].
• Since ACE is identical to kininase II, which inactivates the nonapeptide bradykinin (BK) and related kinins, potentiation of kinins might be responsible for these additional effects of ACE inhibitors. a) In rats made hypertensive by aortic banding, the effect of ramipril in left ventricular hypertrophy (LVH) was investigated [2].
• Ace exposure occurring concurrent with injury would augment the acute-phase response, which would augment the toxic effects of IL-1 and other cytokines, and Ace exposure occurring prior to the injury would suppress or abolish the initial stimulatory effects of IL-1, which would decrease an organism's ability to combat infection or injury [3].
• Diverse effects of Ace inhibitors and angiotensin II receptor antagonists on prevention of cardiac hypertrophy and collagen distribution in spontaneously hypertensive rats [4].
• Thus, tissue Met concentrations in Ace-treated rats were significantly higher than in Met-treated rats and the inhibition of AChE activity was not consistent with the amount of metabolically formed Met, supporting the hypothesis that the Ace protection plays a role in the overall toxicity [5].

Psychiatry related information on Ace

• Presence of serotonin (5-HT) in Ace caused a rapid change of state when injected in rapid- eye-movement sleep (REM) compared with non-REM (NREM) injections [6].
• To characterize further the neuronal activity of AMY during sleep and wakefulness, we recorded single neuronal activity in Ace across behavioral states in freely moving, normally behaving rats [7].

High impact information on Ace

• There are probably two separate but linked quantitative trait loci (QTL) for blood pressure on rat chromosome 10, one marked by Ace and the other marked by Nos2 [8].
• Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea [9].
• Treatment of rats during hypoperfusion. with the angiotensin-converting enzyme (kininase II) inhibitor teprotide increased RBF by 1.1 +/- 0.3 ml/min [10].
• Although small amounts of kininogen-like substrate were found in uterine tissue, detectable kinin levels (greater than 4 pg) could not be found in bathing media during maximal kallikrein-induced contractions or after uterine tissue was incubated with high concentrations of the enzyme in the presence of SQ 20881, a kininase II inhibitor [11].
• Inhibitors of ACE/kininase II enhance insulin sensitivity, an action that is mediated in part by bradykinin (BK) [12].

Chemical compound and disease context of Ace

• 5. Both low dose SP (1 nmol) and capsaicin (1 nmol)-induced hyperalgesia were potentiated by the kininase II inhibitor captopril (100 micrograms) [13].
• The renal responses of magnesium lithospermate B were investigated in the presence or absence of pretreatment with the converting enzyme (kininase II) inhibitor, captopril, in rats with adenine-induced renal failure [14].
• The left coronary bed received the ACE/kininase II inhibitor ramiprilat, alone or in combination with either HOE140 (bradykinin B2 receptor antagonist) or angiotensin II, before induction of regional ischemia (10 min) by discontinuation of flow to the bed [15].

Biological context of Ace

• In an F2 population [F2(S x WKY), n = 159] derived from a cross of S rats with Wistar-Kyoto (WKY) rats, Nos2 alleles did (P = 0.0070), but Ace alleles did not (P = 0.91), cosegregate with blood pressure [8].
• Nine genetic markers, including the angiotensin-converting enzyme (Ace) and Nos2 loci spanning roughly 46 cM on rat chromosome 10, all cosegregated strongly with blood pressure in the F2(S x MNS) population [8].
• Water intake increases with dose of dose of bradykinin, but has an inverted U-shaped relationship with dose of kininase II inhibitor [16].
• This study therefore suggests that Ace would suppress the immune cell numbers in blood, thus decreasing an organism's immunity [3].
• The present findings suggest that the reduction of rat sperm motility and count by Ace can be attributed to its capacity to downregulate AQP1 water channel gene expression [17].

Anatomical context of Ace

• Thus, chronic low-level Ace exposure may impair the lineage commitment in lymphocytes, possibly by altering cytokine signaling in the brain [18].
• Its major efferents from the central nucleus (Ace) to the basal forebrain, hypothalamus and brainstem permit it to influence sleep mechanisms [7].
• Because serotonin introduced into AMY during REM induces short-latency changes of state, we also studied the effects of low frequency (1 Hz) electrical stimulation of the dorsal raphe nucleus (DRN) on Ace neurons [7].
• Dex, however, did not modulate the effects of Ace and Meth on the hypothalamus, which may be attributed to the failure of Dex to modulate the CRF-gene's nGRE regulatory sites [19].
• The endocrine effects of Ace and Met differed from their cholinergic effects, and were not proportional to the amount of Met present in different tissues obtained from the treatment groups [5].

Associations of Ace with chemical compounds

• It was thus discovered that converting enzyme (CE) is identical with the bradykinin-degrading enzyme, kininase II, and CEIs can therefore potentiate the vasodepressor effects of bradykinin and thereby interact with the prostaglandin system [20].
• Angiotensin converting enzyme and kininase-II-like activities in cultured valvular interstitial cells of the rat heart [21].
• We have previously shown that peripheral injection of bradykinin in combination with the kininase II inhibitor, captopril, to rats produces a robust water intake [16].
• We now extend this observation to another kininase II inhibitor, enalapril [16].
• These results indicate that the antihypertensive activity of alacepril is due to the suppression of renin-angiotensin-aldosterone system and the enhancement of kallikrein-kinin-prostaglandin system through the inhibition of ACE (kininase II) activity in vivo [22].

Enzymatic interactions of Ace

• Neutral endopeptidase 24.11 (NEP) cleaves kinins as effectively as kininase I and kininase II [23].

Other interactions of Ace

• Thus, reduced thirst and sodium appetite are found in conjunction with kininase II (angiotensin-converting enzyme) inhibitors in aging rats, possibly because they fail to generate the high levels of circulating renin seen in young rats under these conditions [24].
• Kininase II inhibitors, such as captopril, acutely potentiate drinking to Ang I, but after chronic exposure they may inhibit water intake [25].
• Atrop caused 80-90% inhibition of the effects of IL-1, but caused only 50-65% inhibition of the effects of Ace or Meth on CRF mRNA levels in and CRF release from the hypothalamus [19].
• Acute effects of acephate (Ace) and methamidophos (Met) on acetylcholinesterase activity, endocrine system and amino acid concentrations were studied in rats [5].
• We also studied the effect of a selective inhibitor (captopril, 2.5 mg/kg) of the tachykinin-degrading enzyme kininase II [or angiotensin-converting enzyme (ACE)] on substance P-induced airway vasodilation [26].

Analytical, diagnostic and therapeutic context of Ace

• ACE and kininase-II-like activities in valvular interstitial cells were analysed by high performance liquid chromatography [21].
• Angiotensin-converting enzyme (ACE, kininase II, EC 3.4.15.1) was visualized in unfixed rat brain sections by autoradiography after incubation with a polyclonal goat anti-rabbit lung converting-enzyme antibody and [125I]protein A [27].
• Compensatory increase in adrenomedullary angiotensin-converting enzyme activity (kininase II) after unilateral adrenalectomy [28].
• We studied the effects of the estrous cycle, ovariectomy and estrogen replacement on angiotensin-converting enzyme (ACE) (kininase II, EC 3.4.15.1) and angiotensin II (AT) receptors in the pituitary gland of the female rat [29].
• Because the perfusion medium lacks angiotensinogen, kininogen and aldosterone, the natriuretic action in perfused kidneys may not be related to its inhibitory action on angiotensin I converting enzyme or kininase II [30].

References