Schistosoma mansoni: angiotensin converting enzyme activity in mice under the influence of praziquantel and/or captopril.

Murine schistosomiasis is usually associated with hepatic granulomatous lesions together with high serum and granuloma angiotensin converting enzyme (ACE) activity. Praziquantel (PRZ) which is known to reduce granuloma size was studied to show whether this effect is related to changes in ACE activity. Furthermore, captopril was studied to show whether by inhibiting ACE activity, the drug could also affect granuloma size. PRZ, captopril, and their combination led to significant reduction in liver granuloma. However, in normal mice, captopril was shown to increase rather than decrease serum ACE. The decrease in ACE activity by PRZ was correlated with its curative effect in infected mice. However, in experimentally induced pulmonary granulomata, the drug reduced granuloma size without affecting ACE activity of either serum or granuloma. It may be concluded that reduction in ACE activity may be beneficial as far as diminution of granuloma size is concerned and irrespective of whether there is an active infection or not. The possible use of Captopril as an antihypertensive in bilharzial infections associated with hypertension would probably not adversely affect the granulomatous lesions.     

Effect of acute oral administration of captopril and MK-421 on vascular angiotensin converting enzyme activity in the spontaneously hypertensive rat

Vascular angiotensin converting enzyme (ACE) may be important as a potential site of action for the antihypertensive effect of ACE inhibitors. ACE activity, estimated by hydrolysis of [³H] HipGlyGly, was similar in the aorta, mesenteric and carotid arteries of SHR. ACE activity in veins was not as consistent and was significantly lower in the jugular veins and vena cava of SHR than in the arteries. Nevertheless, ACE activity in all the blood vessels examined, although less than lung ACE activity, was higher than ACE activity found in other tissues such as brain, heart and kidney. Equieffective antihypertensive doses of captopril (10 mg/kg p.o.) and MK-421 (1.0 mg/kg p.o.) dramatically inhibited ACE activity in all the arteries and veins examined. Maximal ACE inhibition occured within 15 minutes after the oral administration of captopril. In contrast, maximal ACE inhibition was slower in onset and of longer duration after MK-421 than after captopril for all the vessels. Thus, relatively high ACE activity can be measured in both arteries and veins from the spontaneously hypertensive rat (SHR) and ACE was dramatically inhibited after antihypertensive oral doses of captopril or MK-421. Furthermore, vascular ACE inhibition can be used to compare the onset and duration of activity of ACE inhibitors; MK-421 has a longer onset and duration in SHR than captopril based on inhibition of ACE in blood vessels.     

ACE activity during the hypotension produced by standardized aqueous extract of Cecropia glaziovii Sneth: A comparative study to captopril effects in rats

To evaluate the effect of the standardized aqueous extract (AE) of Cecropia glaziovii Sneth on the plasma angiotensin I converting enzyme (ACE-EC 3.4.15.1) activity, rats were treated with a single dose of AE (1 g/kg, p.o.) or repeatedly (0.5 g/kg/bid, p.o.) for 60 days. Captopril (50 mg/kg, p.o.) was used as positive control on the same animals. The effects on the blood pressure were recorded directly from the femoral artery (single dose), or indirectly by the tail cuff method (repeated doses) in conscious rats. The plasma ACE activity was determined spectrofluorimetrically using Hypuril-Hystidine-Leucine as substrate. The arterial blood pressure, heart rate and plasma ACE activity were not significantly modified within 24 h after a single dose administration of AE. Comparatively, blood pressure in captopril treated rats was reduced by 7-16% and heart rate was increased by 10-20% from 30 min to 24 h after drug administration. ACE activity after captopril presented a dual response: an immediate inhibition peaking at 30 min and a slow reversal to 32% up-regulation after 24 h. To correlate the drug effects upon repeated administration of either compound, normotensive rats were separated in three groups: animals with high ACE (48.8+/-2.6 nmol/min/ml), intermediate ACE (39.4+/-1.4 nmol/min/ml) and low ACE (23.5+/-0.6 nmol/min/ml) activity, significantly different among them. Repeated treatment with AE reduced the mean systolic blood pressure (121.7+/-0.5 mm Hg) by 20 mm Hg after 14 days. The hypotension was reversed upon washout 60 days afterwards. Likely, repeated captopril administration decreased blood pressure by 20 mm Hg throughout treatment in all groups. After 30 days treatment with AE (0.5 g/kg/bid, p.o.) the plasma ACE activity was unchanged in any experimental group. After captopril (50 mg/kg/bid, p.o.) administration the plasma ACE activity was inhibited by 50% within 1 h treatment but it was up-regulated by 120% after 12 h in all groups. It is concluded that the hypotension produced by prolonged treatment with AE of C. glaziovii is unrelated to ACE inhibition.     

Autocrine regulation of internal anal sphincter tone by renin-angiotensin system: comparison with phasic smooth muscle

The myogenic control mechanisms that govern the basal tone in the internal anal sphincter (IAS) are not known. The present studies determined the autocrine regulation of ANG II in the IAS. The studies were performed in the freshly isolated smooth muscle cells (SMC) of the IAS. We determined the presence of ANG II precursor angiotensinogen (Angen), and the enzymes that convert it into ANG II, using functional, molecular biology, and immunocytochemical studies in rats. ANG II levels in the SMC were determined using ELISA. The IAS SMC generate ANG II at a rate severalfold higher than those from the adjoining smooth muscle of rectum (RSM). RT-PCR data show that IAS exclusively expresses significant higher levels of renin, Angen, and angiotensin-converting enzyme (ACE). These data were confirmed using Western blot analyses and immunocytochemistry. In the IAS SMC, H-77 (10 microM; renin inhibitor) and captopril (1 microM; ACE inhibitor) decreased the basal as well as Angen-increased levels of ANG II. The following functional data corroborate the role of renin-angiotensin system (RAS) in the IAS tone. Angen produced concentration-dependent shortening of the IAS SMC that was inhibited by H-77 and captopril. In addition, H-77 or captopril caused a concentration-dependent fall in the IAS tone vs. nontonic tissues. Basal tone in IAS is partially under the autocrine control of cellular RAS evident by the expression of mRNA coding Angen, renin, and ACE and translation to the respective proteins in the SMC.     

Presence of angiotensin converting enzyme isoforms in larval lepidoptera (Spodoptera littoralis)

In this research the presence of angiotensin converting enzyme (ACE) in larvae of the lepidopteran Spodoptera littoralis was evaluated. Making use of the substrate Abz-FRK-(Dnp)P-OH and the specific inhibitor captopril at 10 microM, ACE activity was determined in a fluorescence assay for intact larvae, hemolymph, head, midgut and dorsal tissue. In dorsal tissue and hemolymph, ACE activity was highest. These data are consistent with a possible role for ACE in contractions of the dorsal vessel and metabolism of circulating peptide hormones in the hemolymph. After the presence of ACE was confirmed, a sequential procedure of anion exchange and size exclusion chromatography was applied to purify ACE from whole wandering larvae (last stage). With this procedure, three different ACE pools were collected that cleaved the fluorogenic substrate Abz-FRK-(Dnp)P-OH. Activity could be inhibited by a final concentration of 2.5 microM captopril. In addition, two out of three samples eluted at different salt concentration and thus ACE 1, 2 and 3 represent at least two different ACE isoforms. These data reveal that ACE is present in S. littoralis and that at least two out of three isolated ACE forms are truly isoforms.     

Seasonal changes in angiotensin converting enzyme activity in male and female frogs (Rana esculenta)

Gonad, lung, kidney and serum angiotensin converting enzyme (ACE) activities were determined by specific substrate hydrolysis in male and female Rana esculenta over 1 year. Ovary ACE activity showed the highest values among the different tissues, with a significant peak (223+/-52 nmol min(-1) mg protein(-1)) in late winter-early spring. Testis ACE activity followed a significant seasonal cycle, increasing from September to peak in April (2.5+/-0.8 nmol min(-1) mg protein(-1)) and then decreased in the post-reproductive period. Lung and kidney ACE activities were not correlated with the annual reproductive cycle phases. In serum a peak of activity was present in the post-reproductive period both in male and female frogs. The present data show a correlation between ACE and the annual reproductive cycle of R. esculenta.     

Effects of continuous angiotensin I-converting enzyme blockade on blood pressure, sympathetic activity and renin-angiotensin system in stroke-prone spontaneously hypertensive rats

The purpose of this study was to examine the effects of continuous angiotensin converting enzyme (ACE) blockade in stroke-prone spontaneously hypertensive rats (sp-SHR) on the renin-angiotensin system and on sympathetic activity. The pressor response to angiotensin II (AII) and norepinephrine (NE) were also examined after chronic blockade of ACE and compared to that of saline-treated controls. Captopril treatment had no effect on body weight. Serum ACE was significantly reduced on day 1; an effect that persisted through day 6 and day 10. Plasma renin activity (PRA) was elevated significantly on day 1 and remained at this high level throughout the 10 day observation period. Plasma NE was not altered by the chronic ACE blockade except on day 1, where there was a slight elevation of plasma NE in both groups. Pressor responses to AII and NE were not changed after chronic captopril treatment. It is observed that chronic inhibition of the renin-angiotensin system with captopril in sp-SHR resulted in a reduction of blood pressure, reduced serum ACE activity and elevated PRA. The constant plasma NE levels suggest that chronic inhibition of the renin-angiotensin system does not affect sympathetic activity. This study also indicates that long term inhibition of ACE does not alter pressor responses to either AII or NE.     

Changes in the activity of the brain renin-angiotensin system and in the functional state of the pituitary-adrenal system of rats under the influence of captopril]

While studying the effect of peroral captopril injections on the activity of renin-angiotensin system (RAS), the activity of angiotensin-converting enzyme (ACE) and angiotensin II content from anterior and mediobasal hypothalamus, medulla and adenohypophysis of intact rats has been established to decrease. Captopril administration decreases ACE activity which increases after hydrocortisone injection in rat medulla and striatum. Captopril results in no potentiation of hormonal effect in hypothalamus and in adenohypophysis where ACE activity decreases following hydrocortisone injection. A decrease in the RAS activity of brain structures and adenohypophysis induced by captopril administration to rats is accompanied by the inhibition of the activity in the pituitary-adrenal system. A decrease in ACTH level and in 11-hydroxycorticosteroids of the rat blood plasma has been determined after single captopril injection in the dosage of 10 and 50 mg/kg of body weight. Duration of the effect depends on the captopril dosage.     

Attenuation of pressor responses to intracerebroventricular angiotensin I by angiotensin converting enzyme inhibitors and their effects on systemic blood pressure in conscious rats

The components of the renin-angiotensin system exist in the brain but their physiological role is uncertain. The effects of two angiotensin converting enzyme (ACE) inhibitors, MK 421 (or its diacid) and captopril, on brain ACE activity, as measured by inhibition of the pressor response to intracerebroventricularly (i.c.v.) administered angiotensin I (AI), and the potential contribution of the central nervous system to their antihypertensive activity were evaluated in the present series of experiments. The diacid of MK 421 (1 and 10 ug) and captopril (3 and 10 ug) given i.c.v. to conscious normotensive rats reduced the pressor response to i.c.v. AI indicating that they can inhibit brain ACE. Responses to AII were unaffected. Oral administration of maximal antihypertensive doses of MK 421 (10 mg/kg) and of captopril (30 mg/kg) to normotensive rats did not attenuate pressor responses to i.c.v. AI indicating that brain ACE was not inhibited under these circumstances. Intracerebroventricular administration of MK 421 diacid, (10 and 30 ug) and captopril (30 and 100 ug) did not lower baseline blood pressure of spontaneously hypertensive rats. These experiments indicate that MK 421 and captopril can inhibit brain ACE but that the central renin-angiotensin system probably does not contribute to their antihypertensive activity.     

Captopril normalises systolic blood pressure in rats with hypertension induced by fetal exposure to maternal low protein diets

Recent studies have demonstrated that the feeding of low protein diets to rats during pregnancy induces hypertension in their offspring. Maternal-diet-induced hypertension has been previously associated with elevated pulmonary angiotensin converting enzyme (ACE) activity. In the present study, the importance of the renin angiotensin system, and in particular ACE, in the maintenance of the hypertensive state, is investigated. Pulmonary and plasma ACE activity were determined in rats of different ages, following in utero exposure to 18 (control) or 9% (deficient) casein diets. No maternal diet induced changes in pulmonary ACE were noted, but at 4 and 13 weeks of age, plasma ACE activity was increased by 34 and 134%, respectively in 9% casein exposed rats relative to controls (P<0.001). Thirteen-week-old rats had significantly raised systolic blood pressure (28 mmHg, P<00.05), and tended to have higher diastolic blood pressure (not significant). These hypertensive animals had slightly raised plasma angiotensin II concentrations (30% higher, not significant), but similar renin activities, when compared with normotensive controls. Treatment of normotensive and hypertensive rats with the ACE inhibitor captopril demonstrated that higher plasma ACE activity may play a major role in the maintenance of maternal-diet-induced hypertension. Whilst normotensive rats showed no significant response to drug treatment, systolic blood pressure in the hypertensive rats fell rapidly to the level observed in the normotensive control group. Blood pressure remained at this lower level until treatment was withdrawn, at which time pressure began to increase slowly, but steadily. A period of 7–8 weeks was required following cessation of captopril administration for the restoration of hypertension.The data are consistent with the hypothesis that components of the renin-angiotensin system, and in particular plasma ACE, are involved in the maintenance of maternal-diet-induced hypertension.     

The frequency of factor V Leiden mutation,ACE gene polymorphism,serum ACE activity and response to ACE inhibitor and angiotensin II receptor antagonist drugs in Iranians type II diabetic patients with microalbuminuria

The aim of present study was to determine if factor V Leiden (FVL) mutation and angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism are associated with diabetic nephropathy (DN) among Kurdish population from Western Iran. This case–control study comprised 144 unrelated adult type 2 diabetic mellitus patients (T2DM) including 72 patients with microalbuminuria and 72 age and sex matched patients without nephropathy. The ACE I/D polymorphism and FVL mutation were detected by polymerase chain reaction (PCR) and PCR–RFLP, respectively. The frequency of FVL G1691A and ACE D allele in T2DM patients with microalbuminuria were 1.6 and 57%, respectively and in normoalbuminuric T2DM patients were 4.9 and 58.3%, respectively (P > 0.05). ACE genotypes affected on serum ACE activity and a better response to ACE inhibitor therapy (captopril) compared to angiotensin II receptor antagonist (losartan) was obtained with significant reduction of ACE activity in diabetic patients without nephropathy carrying DD genotype. However, the beneficial effect of losartan therapy was observed in microalbuminuric patients with II genotype compared to ID and DD genotypes.     

The angiotensin converting enzyme inhibitor captopril reduces oviposition and ecdysteroid levels in Lepidoptera

The role of angiotensin converting enzyme (ACE, peptidyl dipeptidase A) in metamorphic- and reproductive-related events in the Egyptian cotton leafworm, Spodoptera littoralis (Lepidoptera, Noctuidae) was studied by using the selective ACE inhibitor captopril. Although oral administration of captopril had no effect on larval growth, topical administration to new pupae resulted in a large decrease of successful adult formation. Oviposition and overall appearance of adults emerging from treated larvae did not differ significantly from those emerging from non-treated larvae. In contrast, topical or oral administration of captopril to newly emerged adults caused a reduction in oviposition. By evaluating the effect of captopril on ecdysteroid titers and trypsin activity, we revealed an additional physiological role for ACE. Captopril exerted an inhibitory effect on ecdysteroid levels in female but not in male adults. Larvae fed a diet containing captopril exhibited increased trypsin activity. A similar captopril-induced increase in trypsin activity was observed in female adults. In male adults, however, captopril elicited reduced levels of trypsin activity. Our results suggest that captopril downregulates oviposition by two independent pathways, one through ecdysteroid biosynthesis regulation, and the other through regulation of trypsin activity. Apparently, fecundity is influenced by a complex interaction of ACE, trypsin activity, and ecdysteroid levels.     

Circadian Rhythm of Blood Pressure in Congestive Heart Failure and Effects of ACE Inhibitors

In 33 patients with heart failure (NYHA 11-III), the 24-h blood pressure rhythm was examined before and after the titration period of two ACE inhibitors. Blood pressure was measured by the oscillometric method using the blood pressure monitor 90202 from SpaceLabs, Inc. The measurements were taken from 06:OO to 22:OO h every 20 min and from 22:00 to 06:00 h every hour. Patients were randomized to therapy with either captopril (group 1, n = 17) or enalapril (group 2, n = 16). The average daily dosage of captopril was 41 ± 3 mg given in three divided doses (08:00, 12:00, and 17:00 h). The mean dose of enalapril was 8 ± 1 mg once daily (08:00 h). Serum electrolytes, serum creatinine, and plasma renin activity were measured before and during therapy with both ACE inhibitors. Twenty-four-hour blood pressure measurements were taken before and on the fifth day of treatment with ACE inhibitors. Both groups were not different with respect to the degree of heart failure, the concomitant medication, and the 24-h profiles of blood pressure and heart rate before initiation of ACE inhibition. The 24-h blood pressure values on day 5 were consistently below the pretreatment values (p < 0.005) in both groups. Both groups did not differ significantly during ACE inhibition in their 24-h blood pressure and heart rate profiles. In both groups, the mesor of the systolic and diastolic blood pressure decreased significantly by the same degree (by 4.7/5.1 mmg Hg in group 1 and 6.4/4.1 mm Hg in group 2). The systolic/diastolic blood pressure amplitude decreased slightly in both groups. Before treatment, serum sodium, potassium, and creatinine were within the normal range. The increase in potassium (0.5 ± 0.1 mmol/L) reached statistical significance (p < 0.01) only in the captopril group, whereas it was not significant in the enalapril group (0.1 ± 0.1 mmol/L). Serum creatinine was not significantly altered by both ACE inhibitors. No relationship could be found between the changes in serum potassium or creatinine and the mean of the 24-h blood pressure values during ACE inhibition. Captopril and enalapril showed comparable blood pressure profiles and similar effects on renal function at the end of the titration on day 5. It can therefore be concluded that the effects on blood pressure rhythm and renal function are similar with a single daily dose of enalapril compared to captopril given three times daily.     

Characterization and activity of angiotensin-converting enzyme in Holstein semen

The study was designed to perform immunodetection in spermatozoa and seminal plasma, immunolocalization in spermatozoa, and evaluation of the enzymatic activity of angiotensin-converting enzyme (ACE) in the semen of Holstein bulls. We used ejaculates from five bulls as part of a regular collection of semen. The monoclonal anti-ACE antibody recognized a single protein band with 100 kDa in detergent extract prepared from sperm and in seminal plasma. ACE enzymatic activity in sperm was 43.7, 21.3, 45.6, 60.0, and 57.7 mU/mL in bulls 1, 2, 3, 4, and 5, respectively, and 0.3, 2.3, 3.0, 2.3, and 2.6 mU/mL in seminal plasma of the same bulls, respectively. The average percentages of sperm with acrosome reactions after treatment with heparin were 28.3%, 28.6%, 35.2%, 25.0%, and 32.3%, respectively. These values were higher than the percentages of acrosome reactions in controls and the captopril group (P<0.05), although no difference was seen between the captopril and control groups (P>0.05). After 4h of incubation, motility in the control group (32.9%) was significantly higher than that in the heparin (15.7%) and captopril (12.1%) groups. No difference was found in motility after the capacitation assay in the heparin and captopril groups (P>0.05). In conclusion, ACE was immunologically localized in the acrosome of the spermatozoa of Holstein bull, the specific enzymatic activity of ACE in detergent-extracted spermatozoa and seminal plasma was inhibited by captopril, and this ACE inhibitor reduced the percentage of sperm with progressive motility and acrosome reactions after capacitation in vitro.     

Study of antihypertensive mechanism of Tribulus terrestris in 2K1C hypertensive rats: role of tissue ACE activity

Tribulus terrestris is a natural herb used for treating many diseases including hypertension. According to previous reports, aqueous extract of tribulus fruits may have some antihypertensive effect with an unknown mechanism. The present study investigated the antihypertensive mechanism of tribulus in 2K1C hypertensive rats by measurement of circulatory and local ACE activity in aorta, heart, kidney and lung. Four groups of rats were selected; control, sham, operated or hypertensive and tribulus treated hypertensive group. Hypertension was induced using silver clip on renal artery by surgery. Four weeks after surgery, a single daily dose of 10 mg/kg of lyophilized aqueous extract of tribulus fruit were given orally to 2K1C rats for four weeks. ACE activity was determined by high performance liquid chromatography (HPLC). Blood pressure was measured by the tail-cuff method. The systolic blood pressure (SBP) was significantly increased in 2K1C rats compared to control rats. The SBP of tribulus fed hypertensive rats was significantly decreased compared to hypertensive rats. The ACE activity in all tissues of 2K1C rats including: aorta, heart, kidney, lung as well as serum were significantly increased compared to normal rats. The ACE activity in all tissues of tribulus fed hypertensive rats was significantly lower than that of hypertensive rats, which was more pronounced in kidney. These results indicated that there is a negative correlation between consumption of tribulus and ACE activity in serum and different tissues in 2K1C rats.     

ACE inhibitors reduce fecundity in the mosquito,Anopheles stephensi

Angiotensin-converting enzyme (ACE) is a dipeptidyl carboxypeptidase, which cleaves dipeptides and, in some instances, dipeptide or tripeptide amides from the C-terminus of regulatory peptides (e.g. angiotensin I, bradykinin and substance P). The expression of ACE is highly regulated in insects, where it is thought to have a role in the metabolism of peptide hormones involved in regulating reproduction. After a blood meal, ACE activity in the female mosquito Anopheles stephensi, increases four-fold with much of the enzyme finally accumulating in the ovary. In the present study, we have studied the effect on reproduction of adding two selective inhibitors of ACE, captopril and lisinopril, to the blood meal. Both ACE inhibitors reduced the size of the batch of eggs laid by females in a dose-dependent manner, with no observable effects on the behaviour of the adult insect. The almost total failure to lay eggs after feeding on either 1 mM captopril or 1 mM lisinopril, did not result from interference with the development of the primary follicle, but was due to the inhibition of egg-laying. Since very similar effects on the size of the egg-batch were observed with two selective ACE inhibitors, belonging to different chemical classes, we suggest that these effects are mediated by the selective inhibition of the induced mosquito ACE, a peptidase probably involved in the activation/inactivation of a peptide regulating egg-laying activity in A. stephensi.     

Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril

Human somatic angiotensin I-converting enzyme (ACE), a zinc-dependent dipeptidyl carboxypeptidase, is central to the regulation of the renin-angiotensin aldosterone system. It is a well-known target for combating hypertension and related cardiovascular diseases. In a recent study by Bhuyan and Mugesh [Org. Biomol. Chem. (2011) 9, 1356-1365], it was shown that the selenium analogues of captopril (a well-known clinical inhibitor of ACE) not only inhibit ACE, but also protect against peroxynitrite-mediated nitration of peptides and proteins. Here, we report the crystal structures of human testis ACE (tACE) and a homologue of ACE, known as AnCE, from Drosophila melanogaster in complex with the most promising selenium analogue of captopril (SeCap) determined at 2.4 and 2.35 ? resolution, respectively. The inhibitor binds at the active site of tACE and AnCE in an analogous fashion to that observed for captopril and provide the first examples of a protein-selenolate interaction. These new structures of tACE-SeCap and AnCE-SeCap inhibitor complexes presented here provide important information for further exploration of zinc coordinating selenium-based ACE inhibitor pharmacophores with significant antioxidant activity.     

ACE-dependent and chymase-dependent angiotensin II generation in normal and glucose-stimulated human mesangial cells

High glucose (HG) increases angiotensin II (AngII) generation in mesangial cells (MC). Chymase, an alternative AngII-generating enzyme, is upregulated in the glomeruli of diabetic kidneys. In this study, we examined AngII synthesis by human MC via angiotensin-converting enzyme (ACE)-dependent and chymase-dependent pathways under normal glucose (NG, 5 mM) and HG (30 mM) conditions. NG cells expressed ACE and chymase mRNA. Under NG conditions the chymase inhibitor chymostatin reduced AngII levels in cell lysates and in the culture medium, and the ACE inhibitor captopril had no effect. HG induced a 3-fold increase in chymase mRNA and protein but not in ACE mRNA; however, HG induced a 10-fold increase in intracellular ACE activity. The increase in AngII generation induced by HG was found in the cell lysate but not in the culture medium. The rise in intracellular AngII was not prevented by captopril or by chymostatin. Moreover, captopril inhibited extracellular ACE activity but failed to block intracellular ACE activity; these results suggested that captopril was unable to reach intra-cellular ACE. Losartan did not change the intracellular AngII content in either NG or HG conditions, and this lack of change suggested that the increase in AngII was due to intracellular generation. Together these results suggest that chymase may be active in human MC and that both ACE and chymase are involved in increased AngII generation during the HG stimulus by different mechanisms, including an upregulation of chymase mRNA and a rise in intracellular ACE activity, favoring the generation and accumulation of intracellular AngII.     

Stress-Induced Changes in the Activity of Angiotensin-Converting Enzyme in Structures of the Hypothalamo-Hypophyseal-Adrenocortical System of Adrenalectomized Rats

We studied the effects of stress induced by different influences (immobilization and compulsory swimming) on the activity of angiotensin-converting enzyme (ACE, an enzyme of the proteolytic conversion of angiotensin II) in structures of the hypothalamo-hypophyseal-adrenocortical system (HHAS) of unilaterally adrenalectomized (hemiadrenalectomized, HAE) rats. The pattern of stress-induced changes in the activity of ACE depended on the type of stress; rigid daily immobilization of rats for 1 h resulted in more significant shifts. Post-immobilization stress changes in the activity of ACE in the HHAS structures of HAE rats (with a lower basal activity of the endogenous angiotensin system in their hypothalamus) differed from the stress-induced reaction of the enzyme in intact rats. In HAE rats, we also observed inhibition of the activity of a glucocorticoid link of the stress system, as compared with that in intact animals. An inhibitor of ACE, captopril, and a stable analog of leucine-enkephalin, dalargin, when injected before stressing, were capable of decreasing the stress-induced ACE reaction in the hypothalamus and adenohypophysis and of limiting manifestations of the reaction of the adrenals to immobilization. This is interpreted as a proof of the involvement of the components of the angiotensin and enkephalin systems in the formation of the HHAS system to stressing of HAE rats.     

Chronobiologic Evaluation of Angiotensin-Converting Enzyme Activity in Serum and Lung Tissue from Normotensive and Spontaneously Hypertensive Rats

Angiotensin-converting enzyme (ACE) activity in serum and lung tissue from both normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) was determined at six different circadian times. In WKY rats serum ACE varied significantly within 24 h, mainly due to reduced enzyme activity at 12:00 h. In SHR the 24-h profile of serum ACE did not exhibit time-dependent differences. Mean serum ACE activity over 24 h was significantly higher in WKY than in SHR. In lung tissue ACE activity did not depend on the circadian time in either strain. Mean enzyme activity in lung tissue was not different between WKY and SHR. We conclude that circadian changes in the activity of serum and tissue ACE are unlikely to play an important role in the regulation of the circadian blood pressure profile in both normotensive and spontaneously hypertensive rats.