Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin I converting enzyme inhibitors are typically classified as peripheral vasodilators. We studied the effect of captopril and a known vasodilator, hydralazine, on arterial pressure-urinary output relationships in adult spontaneously hypertensive rats to determine whether these drugs produced similar changes in this relationship. Tail-cuff pressure and 24-hour urine output and sodium excretion were measured under steady state conditions during ingestion of tap water or saline (1% NaCl) ad libitum. Sodium intake increased seven to nine times when rats drank saline, but in the absence of drug treatment, tail-cuff pressure was not altered significantly (water, 213 +/- 3 vs saline, 220 +/- 5 mm Hg). Daily administration of captopril (100 mg/kg p.o.) or hydralazine (15 mg/kg p.o.) for 2 weeks lowered tail-cuff pressure significantly (175 +/- 3 and 166 +/- 3 mm Hg, respectively; p less than 0.01) while rats drank tap water. Continued administration of hydralazine plus 2 weeks of drinking saline did not alter tail-cuff pressure (162 +/- 4 mm Hg), but with the addition of saline during captopril treatment, tail-cuff pressure was elevated significantly (210 +/- 5 mm Hg; p less than 0.01). Thus, hydralazine produced a parallel shift of the arterial pressure-urinary output relationship along the pressure axis. In contrast, captopril produced a marked change in the slope of this relationship, making arterial pressure extremely salt-sensitive. The results suggest that the two drugs have different effects on the mechanisms that contribute to the long-term control of arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1987 Dec
PMID:Effect of captopril and hydralazine on arterial pressure-urinary output relationships in spontaneously hypertensive rats. 331 99

Angiotensin I converting enzyme (ACE) participates not only in the regulation of the extracellular fluid volume and blood pressure but also in the control of proliferating processes in the human organism. The favourable effect of ACE inhibitors in the treatment of essential hypertension may be caused also by their antiproliferative effect. The development of essential hypertension is probably of polygenic origin. The gene for ACE, and its alleles encountered commonly in the population is involved in the pathophysiology of systemic hypertension by acting on the dynamic properties of processes in the organism which regulate changes of the extracellular fluid volume and proliferation. Therefore it is necessary, when treating systemic hypertension with ACE inhibitors, to pay attention to monitoring of the blood pressure and organ changes. The relationship with blood pressure assessed by conventional methods need not be close. The antiproliferative effect of ACE inhibitors may be favourable in the treatment of hypertension and its clinical use in oncology may be taken into consideration.
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PMID:[Angiotensin I converting enzyme: what results from new findings] . 1104 20

The Angiotensin I converting enzyme (ACE, EC 3.4.14.1, kininase II) and neutral endopeptidases (NEP, NEP 24.11) are mechanistically related metallopeptidases. They play a key role in the regulation of blood pressure, body fluid homeostasis and cell growth. Therefore, they are implicated in the pathogenesis of arterial hypertension, congestive heart failure, left ventricular remodeling after myocardial infarction and other cardiovascular diseases. Furthermore, since these two metallopeptidases possess some subsite and substrate similarities, as indicated by their interaction with certain mercaptoalkanoyl inhibitors, they are regarded as an important common target for pharmacological inhibition with a single drug. MDL 100240 is a pro-drug that, upon conversion to MDL 100173, acts as a potent dual inhibitor of ACE and NEP with a balanced activity on both enzymes. Only very limited pharmacokinetic studies with MDL 100240 have been published. These studies used a high pressure liquid chromatography method with UV absorbance detection to quantify the drug. According to the studies in dogs the terminal t(1/2) of MDL 100173 was 35.7 h. The area under the curve for total MDL 100173 was nearly 10-fold greater than the sum of the areas under the curve for MDL 100240 and for unconjugated MDL 100173. These results support the hypothesis that MDL 100240 is hydrolyzed in plasma to the active thiol, MDL 100173, which is rapidly conjugated with endogenous plasma thiols thus providing a pathway for elimination. Studies in vivo in experimental models of hypertension and congestive heart failure confirmed the vasodilatory and natriuretic effects of MDL, which appear to be independent of the degree of activation of the renin-angiotensin-aldosterone system. In addition, MDL 100240 showed an impressive effectiveness both in preventing and in regressing hypertension-induced vascular remodeling and cardiac hypertrophy. Accordingly, MDL 100240 is being developed for the treatment of cardiovascular diseases, including hypertension and congestive heart failure. If the promises of this novel therapeutic strategy are fulfilled, clinical trials are expected to demonstrate advantages of MDL 100240 over pure ACE inhibitors.
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PMID:Dual ACE and NEP inhibitors: a review of the pharmacological properties of MDL 100240. 1259 17

Angiotensin I converting enzyme (ACE) inhibitory peptides cause an antihypertensive effect if they reach the systemic circulation. This was investigated for the high ACE inhibitory activity present in peas and whey in vitro gastrointestinal digests. The samples retained high ACE inhibitory activity when incubated in Caco-2 homogenates or rat intestinal acetone powder, both sources of small intestine peptidases. Only little ACE inhibitory activity was transported through Caco-2 cell monolayers in 1 h. As the Caco-2 model is tighter than intestinal mammalian tissue, sufficient absorption of these peptides might occur in vivo. After intravenous administration of 50 mg protein kg(-1) BW in spontaneously hypertensive rats (SHR), pea digest exerted a transient, but strong antihypertensive effect of 44.4 mmHg. Whey digest exerted no effect at this dose. These results suggest that pea digest could be a promising source of ACE inhibitory peptides for use in the prevention and treatment of hypertension.
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PMID:In vitro intestinal transport and antihypertensive activity of ACE inhibitory pea and whey digests. 1636 Nov 82

Angiotensin I converting enzyme (ACE) inhibitory peptide was isolated from tuna dark muscle hydrolysate prepared by alcalase, neutrase, pepsin, papain, alpha-chymotrypsin, and trypsin, respectively. Among hydrolysates, the pepsin-derived hydrolysate exhibited the highest ACE I inhibitory activity versus those of other enzyme hydrolysates. The structure of the peptide was identified to be Trp-Pro-Glu-Ala-Ala-Glu-Leu-Met-Met-Glu-Val-Asp-Pro (molecular weight 1581 Da) by time of flight mass spectrometry/mass spectrometry analysis, and the IC 50 value of the peptide was 21.6 microM. The Lineweaver-Burk plots revealed that the peptide acts as a noncompetitive inhibitor, and the inhibitor constant ( K i) was calculated as 26.6 microM using the secondary plots. The peptide had an antihypertensive effect according to the time-course measurement after oral administration to spontaneously hypertensive rats. Maximal reduction was detected 3 h after oral administration at a dose of 10 mg/kg of body weight. These results suggest that the peptide derived from tuna dark muscle would be a beneficial ingredient for functional food or pharmaceuticals against hypertension and its related diseases.
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PMID:Antihypertensive effect of angiotensin i converting enzyme-inhibitory peptide from hydrolysates of Bigeye tuna dark muscle, Thunnus obesus. 1789 58

Hypertension is one of the most common worldwide diseases that afflict humans. Angiotensin I converting enzyme (ACE) catalyzes the formation of vasoconstrictor, angiotensin II, and the inactivation of vasodilator, bradykinin. The influences of ACE on blood pressure make it an ideal target clinically and nutritionally in the treatment of hypertension. A number of animal food-derived peptides have been reviewed about their in vitro and in vivo ACE inhibitory activities. The aim of this review is to discuss the plant food-derived angiotensin I converting enzyme (ACE) inhibitory peptides from sources, production, purification, and structure to in vitro and in vivo activities.
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PMID:Plant food-derived Angiotensin I converting enzyme inhibitory peptides. 1944 87

Angiotensin I converting enzyme (ACE) inhibitory peptide was isolated from the marine rotifer, Brachionus rotundiformis. ACE inhibitory peptides were separated from rotifer hydrolysate prepared by Alcalase, alpha-chymotrypsin, Neutrase, papain, and trypsin. The Alcalase hydrolysate had the highest ACE inhibitory activity compared to the other hydrolysates. The IC(50) value of Alcalase hydrolysate for ACE inhibitory activity was 0.63 mg/ml. We attempted to isolate ACE inhibitory peptides from Alcalase prepared rotifer hydrolysate using gel filtration on a Sephadex G-25 column and high performance liquid chromatography on an ODS column. The IC(50) value of purified ACE inhibitory peptide was 9.64 microM, and Lineweaver-Burk plots suggest that the peptide purified from rotifer protein acts as a competitive inhibitor against ACE. Amino acid sequence of the peptide was identified as Asp-Asp-Thr-Gly-His-Asp-Phe-Glu-Asp-Thr-Gly-Glu-Ala-Met, with a molecular weight 1538 Da. The results of this study suggest that peptides derived from rotifers may be beneficial as anti-hypertension compounds in functional foods resource.
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PMID:Purification and characterization of angiotensin I converting enzyme inhibitory peptides from the rotifer, Brachionus rotundiformis. 1954 Jan 10

Angiotensin I converting enzyme (ACE) inhibitory and antioxidant peptides are receiving attention due to their beneficial effects in the prevention/treatment of hypertension. The objective was to explore the effect of high hydrostatic pressure (HP) on proteolysis by different proteases and the release of bioactive peptides from lentil proteins. Pressurisation (100-300 MPa) enhanced the hydrolytic efficiency of Protamex, Savinase and Corolase 7089 compared to Alcalase. Proteolysis at 300 MPa led to a complete degradation of lentil proteins and increased peptide (<3 kDa) concentration by all enzymes. Proteolysis at 300 MPa by Savinase gave rise to lentil hydrolysates (S300) with the highest ACE-inhibitory and antioxidant activities that were retained upon in vitro gastrointestinal digestion. The peptides responsible for the multifunctional properties of S300 hydrolysate were identified as different fragments from storage proteins and the allergen Len c 1. These results support the potential of HP as a technology for the cost-effective production of bioactive peptides from lentil proteins during enzymatic proteolysis.
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PMID:High-pressure improves enzymatic proteolysis and the release of peptides with angiotensin I converting enzyme inhibitory and antioxidant activities from lentil proteins. 2530 63

Angiotensin I converting enzyme (ACE) gene is one of the most-studied candidate genes related to essential hypertension (EH). Pulse pressure (PP) may reflect vascular stiffness, especially in patients with EH, and has been used to predict EH. Previous evidence has indicated that obesity is a traditional risk factor of hypertension. The aim of the present study was to investigate the interaction between the obesity status and ACE gene polymorphisms on the development of high level of PP. A total of 1980 adults (1024 hypertensive and 956 normotensive) were included in this study and genotyped for ACE gene polymorphisms. The results showed that rs4343 and rs4351 in ACE gene were risk factors of high level of pulse pressure (p < 0.05). We also detected positive interactions between the two SNPs and obesity status in the pathway of high level PP.
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PMID:Association of angiotensin-converting enzyme gene polymorphism with pulse pressure and its interaction with obesity status in Heilongjiang province. 2954 99