Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of hypertension in the elderly has so far mainly been based on clinical judgment and very few large controlled trials. During the last year several large new trials have been published, the so-called STOP-Hypertension, SHEP, and MRC trials. All have shown that drug treatment of hypertension in the elderly (65-85 years) with permanent diastolic hypertension or isolated systolic hypertension reduces stroke incidence. Most patients have needed combined drug treatment with diuretics and beta-blockers. When thiazide diuretics are used, serum potassium should be followed very closely and most likely amiloride should be added to the thiazide therapy, since this was done both in the STOP and the MRC trials. Since many elderly patients with hypertension suffer from other diseases that might represent contraindications to thiazide diuretics or beta-blockers, the choice of drug must be made after careful clinical evaluation. With the newer classes of antihypertensive agents (calcium antagonists, ACE inhibitors and alpha-blockers) side effects are probably seen less often, but long-term data on morbidity and mortality are still lacking.
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PMID:Treatment of hypertension in the elderly--what have we learned from the recent trials? 129 75

Earlier studies on the cardiovascular effects of intracerebroventricular (i.c.v.) administration of angiotensin converting enzyme (ACE) inhibitors implicate angiotensin II (AII) present in the central nervous system in the pathogenesis of hypertension. We have now examined whether central AII contributes to the maintenance of established hypertension in adult stroke-prone spontaneously hypertensive rats (SHRSP). The ACE inhibitor, enalaprilat, was infused i.c.v. for two weeks at a rate of 5 micrograms/h via osmotic minipumps. Control rats were either untreated or infused with saline. Mean arterial pressure (MAP), measured via an indwelling catheter, fell within 24 h in the enalaprilat-treated rats and remained at least 30 mmHg lower than in controls. This difference persisted after intravenous (i.v.) administration of a vasopressin (AVP) antagonist but was eliminated by subsequent ganglion blockade with i.v. pentolinium. Without prior administration of the AVP antagonist, however, the reductions of MAP after pentolinium were smaller. The reduction was still attenuated in treated rats compared with controls but there was a significant difference in the residual MAP. Circulating catecholamine levels were reduced by central ACE inhibition. However, pressor responsiveness to i.v. phenylephrine was unaffected. The results suggest that, in SHRSP, central ACE inhibition lowers blood pressure by reducing sympathetic outflow, implying that central AII has a tonic sympathoexcitatory effect in this strain.
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PMID:Chronic central administration of enalaprilat lowers blood pressure in stroke-prone spontaneously hypertensive rats. 133 Dec 22

The hemodynamic effects of imidapril, a novel nonsulfhydryl angiotensin-converting enzyme inhibitor, were examined in anesthetized dogs by the intravenous injection of its active metabolite 6366A ((4S)-3-((2S)-2-[N-((1S)-1-carboxy-3- phenylpropyl)amino]propionyl)-1-methyl-2-oxoimidazolidine-4-carboxylic acid, CAS 89371-44-8) and were compared to those of enalaprilat. 6366A (1-100 micrograms/kg) reduced the blood pressure and total peripheral resistance in a dose-dependent manner, while causing no marked changes in heart rate, LV dp/dtmax, and pulmonary arterial pressure. The cardiac output and stroke volume were slightly increased. Blood flow in the common carotid artery, the vertebral artery, and the femoral artery was reduced or tended to decrease, while the superior mesenteric arterial blood flow was increased. These effects were similar to those of enalaprilat. 6366A did not inhibit the pressor response of angiotensin II, but markedly inhibited that of angiotensin I, and the effects of 6366A on regional blood flow were opposite to those of angiotensin II. Thus, 6366A appears to produce its hemodynamic effects by angiotensin converting enzyme inhibition, as does enalaprilat. 6366A also tended to decrease myocardial oxygen consumption. These results suggested that the hemodynamic effects of imidapril on the heart and on regional blood flow are similar to those of enalapril.
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PMID:Acute hemodynamic effects of the active metabolite of imidapril, (4S)-3-((2S)-2-[N-((1S)-1-carboxy-3-phenyl-propyl)amino]propionyl)-1- methyl-2-oxoimidazolidine-4-carboxylic acid, and enalaprilat in anesthetized dogs. 133 27

Pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), blood pressure (BP) were monitored before and after hypoxia, Captopril and Nitrendipine injected (7 mg/kg and 100 micrograms/kg) in group A(n = 9), and group B(n = 7) respectively results showed that during hypoxia PAP in all the pigs increased significantly (P < 0.05), compared with normoxia, and after captopril and nitrendipine intravenous injection, the PAP dropped significantly (from 3.76 +/- 0.25 to 3.43 +/- 0.1 kPa versus from 4.21 +/- 0.19 to 3.18 +/- 0.17 kPa. ACE in captopril group was significant reduced P < 0.05 (58.4 +/- to 27.0 +/- 3.0 mumol.min-1/L), but in nitrendipine group was not markedly changed (P > 0.05), we found that reducing the degree of PAP and its duration time, lowered the pulmonary vascular resistance (PVR) and right ventricle stroke index (RVSWI), also improved capacity of oxygen delivery. Nitrendipine was better than captopril, maybe it is an useful drug for patients with pulmonary hypertension.
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PMID:[Comparative studies between the effects of captopril and nitrendipine on the hemodynamics and angiotensin converting enzyme of pigs with acute hypoxic pulmonary hypertension]. 133 19

1. The angiotensin converting enzyme (ACE) activity of spontaneously hypertensive (SHR) and spontaneously hypertensive stroke-prone (SHRSP) rats was compared to the ACE activity of normotensive Wistar-Kyoto rats (WKY). 2. ACE activity was assessed indirectly in conscious unrestrained rats using the equipressor response end point to simultaneously calculate the extent of conversion of angiotensin I (AI) to angiotensin II (AII) and the pulmonary degradation of bradykinin (BK). 3. The pulmonary degradation of BK was significantly elevated (99.4%) in SHR rats whereas the elevation was not significant in SHRSP rats (99.2%) compared to WKY rats, even though the pulmonary inactivation of BK in WKY rats was higher (98.6%) than in normotensive Wistar rats (95.6% and 97.5%) previously studied. 4. Blood pressure responsiveness to intra-aortically injected BK (bolus injection and infusion) was markedly increased in SHR and SHRSP rats with no change in reactivity to sodium nitroprusside. 5. Conversion of AI to AII assessed by the equipressor doses of the hormones which produced a 20-mmHg rise in blood pressure was markedly elevated in SHR (86 +/- 4%) and SHRSP (80 +/- 7%) rats when compared to WKY rats (38 +/- 4%). 6. The marked increase in conversion of AI to AII in hypertensive animals, accompanied by an increased pulmonary degradation of BK in SHR rats, suggests that ACE activity is increased in conscious SHR and SHRSP rats and may participate in the genesis of hypertension in this model of genetic hypertension.
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PMID:Angiotensin converting activity assessed in vivo is increased in hereditary hypertensive rats. 134 16

The actions of angiotensin II can be described in terms of the three paradigms listed in Table 1. According to the first paradigm (organ physiology), angiotensin II is a pressor, while the second (cell biochemistry) views it as an extracellular messenger that, by promoting Ca2+ release within cells, causes vasoconstriction and a weak positive inotropic response by the heart. However, neither of these paradigms fully explains the remarkable ability of angiotensin converting enzyme inhibitors to improve the prognosis for patients with heart failure. To account for these clinical effects of angiotensin converting enzyme inhibitors, we will probably need to invoke the third paradigm (gene expression), which views angiotensin II as a growth factor that promotes and modifies protein synthesis. Angiotensin II, therefore, should probably not be viewed simply as a vasoconstrictor with a side effect to promote hypertrophy, but instead as a growth factor that, because it utilizes Ca2+ to mediate its effects on gene expression, also increases smooth muscle tone and myocardial contractility. This view of angiotensin II as a growth factor helps us to understand the clinical benefit of angiotensin converting enzyme inhibitors as arising from inhibition of maladaptive changes in the failing heart (gene expression) as well as from the reduced afterload (organ physiology) that results from decreased smooth muscle tone (cell biochemistry).
Heart Dis Stroke
PMID:Is angiotensin II a growth factor masquerading as a vasopressor? 134 1

Renal arterial disease occurs in 3-5% of patients with systemic hypertension. It is important to determine the type of lesion by arteriography to understand the natural history of the specific disease and to choose appropriate therapy. Some have questioned why arteriography should be performed if an operation or percutaneous transluminal renal angioplasty is not considered. One must keep in mind that if the arteriographic characteristics are known, the specific lesion and its course may be predicted, resulting in better management of the disease. In patients with a unilateral lesion angiotensin converting enzyme inhibitors are efficacious, but calcium antagonists may also be used. However, if therapy does not provide optimum control of blood pressure or the impairment of renal function progresses, then percutaneous transluminal renal angioplasty or surgery should be reconsidered.
Heart Dis Stroke
PMID:Hypertension due to renal arterial disease. 134 12

The cardinal hemodynamic disorder in established essential hypertension is increased total peripheral resistance. During exercise, the increase in stroke volume of the heart is abnormal. A 20-year follow-up study of the hemodynamics in essential hypertension demonstrated a progressive increase in total peripheral resistance and deterioration of the heart pump function. Long-term treatment with antihypertensive agents modifies the circulatory system in different ways. Vasodilators (angiotensin converting enzyme inhibitors, alpha 1-blockers, and calcium antagonists) all reduce total peripheral resistance, and in general, cardiac output, heart rate, and stroke volume remain unchanged. Calcium antagonists like verapamil and diltiazem reduce the heart rate approximately 10% during exercise, but since stroke volume increases, cardiac output is unchanged. Chronic treatment with conventional beta-blockers induces a permanent reduction in cardiac output and heart rate during exercise. In contrast, carvedilol--a beta 1,beta 2-blocker with alpha 1-blocking activity--prevents the immediate increase in total peripheral resistance during acute beta-blockade. In 19 patients followed by hemodynamic measurements over 6-9 months, blood pressure was well controlled by carvedilol. During exercise, total peripheral resistance decreased 6% (P less than 0.05), and the reductions in heart rate and cardiac index were less than on conventional beta-blockade. Echo-Doppler studies showed a significant reduction in the intraventricular septum of 13%.
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PMID:Long-term hemodynamic effects of antihypertensive treatment. 135 Apr 86

The antihypertensive and hemodynamic effects of lisinopril and atenolol were evaluated in 21 patients with mild-to-moderate essential hypertension. Left ventricular systolic and diastolic performances were assessed prior to and following treatment by first-pass radionuclide cineangiography at rest and during peak upright bicycle exercise. Both lisinopril and atenolol treatment significantly reduced the blood pressure. Lisinopril therapy was associated with a reduction in systemic vascular resistance and left ventricular end-diastolic and end-systolic volumes but no change in stroke volume, cardiac output, peak ejection rate, peak filling rate, time to peak ejection rate, or time to peak filling rate. In contrast, atenolol therapy was associated with an increase in end-diastolic volume and stroke volume but no change in cardiac output; the left ventricular peak ejection and peak filling rates were decreased by atenolol treatment. Although both lisinopril and atenolol each significantly reduced the blood pressure, lisinopril had no effect on left ventricular systolic or diastolic performance; in contrast, atenolol decreased both systolic and diastolic parameters of ventricular performance. Left ventricular function may be affected in significantly different ways despite apparent similarities in blood pressure control in patients who respond to angiotensin converting enzyme inhibition or beta-adrenergic receptor blockade. Differences in hemodynamic response to an antihypertensive agent may be important in the selection of a drug for the treatment of subsets of patients with cardiac function abnormalities.
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PMID:Comparison of the cardiac and hemodynamic effects of lisinopril and atenolol in patients with hypertension: therapeutic implications. 138 Oct 12

Left ventricular hypertrophy is more common in hypertensive individuals than in normotensive persons. Its presence in hypertensive patients is associated with an increased incidence of ventricular arrhythmias, myocardial infarction, congestive heart failure, stroke and cardiovascular mortality. Echocardiography is more sensitive than electrocardiography in detecting left ventricular hypertrophy. Echocardiographic evidence of this condition in patients with borderline hypertension may identify those who need treatment. Weight reduction and drug therapy can prevent or reverse ventricular hypertrophy in hypertensive patients. Recent studies suggest that some antihypertensive drugs are more effective than others in reducing left ventricular hypertrophy. These agents include beta-adrenergic blockers, angiotensin converting enzyme inhibitors, calcium channel blockers and sympatholytic agents. Although little evidence exists to show that reduction of left ventricular mass decreases cardiovascular morbidity and mortality, avoidance of antihypertensive agents that may aggravate hypertrophy would seem prudent.
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PMID:Left ventricular hypertrophy and antihypertensive therapy. 138 79


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