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)

The four most popular classes of antihypertensive drugs may all be considered suitable choices when initiating treatment for hypertension. The practitioner must decide which agent is appropriate for each individual patient. The main goal of treatment should be to prevent coronary events and stroke, while preserving quality of life. A 40% reduction in stroke can probably be achieved with any antihypertensive treatment, a reduction in coronary events is much harder to achieve. Available evidence from studies in men, summarized in this review, indicates that beta-blockade is superior to thiazide diuretics for the prevention of coronary events. Clinical trials have not yet produced long-term prognostic data on the effects of ACE-inhibitors or calcium antagonists on coronary events in hypertensive patients. A recent review on calcium antagonists in post-MI patients concluded that the results were disappointing, as pooled data actually showed a trend towards increased mortality with calcium antagonists as compared with placebo. Because of the large number of hypertensive patients at increased risk for coronary events in the community, the difference observed in coronary events between beta-blockade and other first-line drugs in hypertension (24%) may have important implications for clinical practice. This overall conclusion, however, has to be accepted with some reservations in view of the following observations. Firstly, no reduction in sudden death has been observed with the hydrophilic beta-blockers. Secondly, no reduction in coronary mortality in the smoking subgroup has been observed with the non-selective beta-blockers. Thus, it seems that the prevention of coronary events is more likely to be observed in patients given beta-blockers with certain pharmacological characteristics: relative lipophilicity, which enables passage of the beta-blocker through the blood-brain barrier to exert effects on pertinent central nervous beta 1-receptors. This is potentially useful in reducing the risk of sudden death. The addition of beta 1-selectivity is important for the risk reduction in smokers. Cardioselectivity is also an advantage in relation to side-effects and quality of life. The reduced risk for coronary events with certain beta-blockers is probably independent of the reduction in blood pressure: possible mechanisms studied are cardiac anti-ischaemic effects, antifibrillatory effects, antiatherosclerotic and anti-thrombotic effects.
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PMID:Reducing the risk for coronary heart disease and stroke in hypertensives--comments on mechanisms for coronary protection and quality of life. 154 19

Age-related changes (e.g., decrease in plasma renin activity and total body potassium, increase in plasma catecholamines, volume depletion) need to be taken into account when selecting an antihypertensive agent for the elderly patient. A number of large scale clinical trials (e.g., Systolic Hypertension in the Elderly Program, Veterans Administration Cooperative Study, European Working Party on High Blood Pressure in the Elderly) have demonstrated that antihypertensive therapy with diuretics substantially reduced cardiovascular mortality and stroke incidence. However, since diuretics, even potassium-sparing agents, may induce hypokalemia, newer antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors and calcium antagonists) may also be appropriate as first-line monotherapy for this patient population. ACE inhibitors are effective antihypertensive agents and are associated with a lower rate of adverse effects than diuretics, beta blockers, and centrally acting agents. Nevertheless, periodic monitoring of serum potassium, creatinine levels, and renal function is advisable. An important feature of calcium antagonists is that they lower blood pressure with no negative effect on serum lipids or glucose metabolism. Typically, they have few side effects, peripheral edema being the most commonly reported. A recent double-blind randomized study comparing a new sustained release nifedipine formulation and the ACE inhibitor lisinopril found the 2 drugs equivalent in efficacy with no differences in the rate of adverse events.
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PMID:Hypertension in the elderly with a special focus on treatment with angiotensin-converting enzyme inhibitors and calcium antagonists. 157 76

Antihypertensive therapy influences kidney function by different mechanisms depending on the mode of action of the drug used. The GFR is improved by calcium entry blockers and ACE inhibitors, unaffected by vasodilators, alpha-blockers and centrally acting sympatholytics and impaired by beta-blockers. The same is true for renal blood flow and is due to changes of renal vascular resistance. Renal sodium excretion is impaired mostly by vasodilators, by alpha-blockers, sympatholytics and beta-blockers; in contrast, calcium entry blockers and ACE inhibitors acutely induce natriuresis. The RAAS is stimulated by vasodilators, unaffected by alpha-blockers and sympatholytics and suppressed by beta-blockers. Plasma catecholamines are stimulated by vasodilators and suppressed by centrally acting sympatholytics and unaffected by the others. Induction of acute renal functional impairment is reported for ACE inhibitors under conditions of compromised renal perfusion pressure such as in renal artery stenosis. These data from the literature reviewed are supported by our own experimental data on sodium balance under different drugs and micropuncture data in experimental renal artery stenosis. To achieve effective antihypertensive treatment with a low profile of side effects, careful monitoring of renal function seems to be mandatory.
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PMID:Influence of antihypertensive therapy on renal function. 159 4

Cytosolic [Ca2+] can be increased by influx of the ion from the extracellular compartment, Ca2+ release from intracellular storage sites, and/or a reduced activity of active transport processes for Ca2+ extrusion or sequestration. Organic calcium antagonists block transmembrane calcium entry and, therefore, can be utilized to evaluate the importance of calcium influx in the regulation of renal hemodynamics. Recent studies indicate that calcium antagonists selectively vasodilate preglomerular arterioles, leading to increases in renal blood flow (RBF), glomerular filtration rate (GFR) and glomerular pressure. In contrast with angiotensin converting enzyme inhibitors and other vasodilator agents, calcium antagonists primarily influence the component of renal vascular resistance responsible for autoregulation, potently attenuating autoregulatory efficiency. Calcium antagonists also block the afferent arteriolar vasoconstriction elicited by angiotensin II, while not influencing the efferent arteriolar vasoconstriction evoked by this peptide. Tubuloglomerular feedback (TGF)-mediated vasoconstrictor responses are also abolished by calcium antagonists, indicating that the TGF effector mechanism may require transmembrane calcium influx into the smooth muscle cells of the afferent arterioles. These observations provide compelling evidence that calcium influx, through pathways which are influenced by organic calcium antagonists, is an integral component of the afferent arteriolar vasoconstriction elicited by a variety of stimuli, while efferent arteriolar vasoconstriction appears to depend on other calcium access pathways.
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PMID:Effects of calcium antagonists on renal hemodynamics and glomerular function. 161 67

The pathogenesis of progressive renal disease includes systemic hypertension and intrarenal factors that may be hemodynamic or metabolic in origin and involve mediators of inflammation. Most current information derives from experiments in rodents. In other species (rabbit, dog, baboon) subjected to renal mass reduction, a greater variety of pathologic changes is apparent than in rats. Clinical trials at controlling progression of renal disease are compounded by numerous factors; and it is not evident that extrapolation can safely be made from results of animal studies to human disease. The mechanism(s) of renal disease progression in humans, therefore, remain largely unknown. Current therapeutic recommendations in patients with chronic renal disease include limitation of phosphorus absorption, correction of lipid abnormalities and control of systemic blood pressure. The latter can be achieved with a variety of agents some of which, like angiotensin converting enzyme inhibitors and calcium antagonists, may be preferred because of specific intrarenal effects.
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PMID:Progression of renal disease: current concepts and therapeutic approaches. 161 70

Therapeutic approaches to the management of heart failure have traditionally focused on shortterm hemodynamic and symptomatic goals, but present evidence suggests that most therapeutic decisions have long-term consequences. Treatment may change the rate of disease progression, modify the need for additional therapy, influence the number of hospitalizations, and alter the risk of death. However, there may be little relation between a drug's short-term effect on cardiac function or cardiovascular symptoms and its long-term effect on survival. Some therapeutic interventions favorably influence the outcome of patients with heart failure, even though they exert negative inotropic effects; others adversely affect the outcome of patients, even though they markedly improve cardiac performance. This discordance might be explained if the most important predictor of response to a therapeutic intervention in heart failure were the effect of the pharmacologic agent on neurohormonal systems rather than on hemodynamic variables. In general, drugs that decrease the effects of the sympathetic nervous system (digitalis glycosides) and the renin-angiotensin system (angiotensin-converting enzyme [ACE] inhibitors) reduce the risk of worsening heart failure. Conversely, drugs that potentiate the effects, or increase the activity, of the sympathetic nervous system (phosphodiesterase inhibitors) or the renin-angiotensin system (calcium antagonists) increase cardiovascular morbidity and mortality. These observations suggest that physicians should no longer focus on short-term hemodynamic or symptomatic goals in the treatment of heart failure but, instead, should manage patients to improve both the quality and quantity of life.
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PMID:Long-term strategies in the management of heart failure: looking beyond ventricular function and symptoms. 162 88

The authors investigated in ten patients with essential hypertension changes in the membrane transport of sodium in red blood cells and the intracellular calcium content of thrombocytes during the control period during treatment of hypertension with central sympatholytics and after three-week treatment with an inhibitor of the angiotensin converting enzyme (ACE), enalapril. The effect of enalapril in hypertonic patients was manifested by a rise of the renin plasma activity and the potassium concentration and a reduction of the sodium plasma concentration which corresponds to the inhibition of angiotensin II. The intracellular calcium and sodium content was unaltered. In 8 of 10 patients after enalapril treatment increased values of Vmax for Na(+)-K+ cotransport occurred, incl. 6 patients where at the same time a rise of Vmax Na(+)-Li+ countertransport was recorded.
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PMID:[Membrane transport of cations in erythrocytes during treatment of essential hypertension with angiotensin-converting enzyme inhibitors]. 163 92

1. The possibility of an acute pharmacokinetic or pharmacodynamic interaction between the ACE inhibitor ramipril and the calcium antagonist felodipine was examined in 12 normotensive male volunteers. 2. Ramipril (5 mg) and felodipine ER (10 mg) were administered orally in a double-blind, randomised, placebo-controlled, Latin square design to fasting subjects. 3. There was no evidence of a pharmacokinetic interaction between agents. The concentration-time profiles remained unaltered by coadministration of both agents. 4. Plasma ACE inhibition by ramiprilat was unaffected by concurrent felodipine. The trend towards increased fractional sodium excretion after felodipine was not influenced by ramipril. Plasma renin activity, aldosterone and catecholamines remained unaltered. 5. Combination therapy produced a statistically significant fall in blood pressure supine and erect which was not evident with monotherapy. The reflex tachycardia associated with felodipine monotherapy was significantly attenuated by the coadministration of ramipril. 6. This study presents further evidence for the effective combination of ACE inhibitors and calcium antagonists to lower blood pressure. The reflex tachycardia associated with calcium antagonist therapy can be significantly reduced by coadministration with sustained antihypertensive effect.
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PMID:A study of the acute pharmacodynamic interaction of ramipril and felodipine in normotensive subjects. 164 21

Cocaine abuse can cause cardiovascular damage leading to hypertension, myocardial ischaemia and infarction. This might be partly due to the effects of cocaine on the microcirculation about which little is known, although its effects on the macrovessels are well documented. Accordingly, we used in vivo videomicroscopy to study the vasoconstrictive effect of cocaine on arterioles of different diameter. They were classified into three orders (A2, A3, A4) according to their position in the microvascular network and their diameter. Since calcium antagonists have been reported to exert a protective effect against the cardiovascular disorders induced by cocaine, we tested the hypothesis that this protective action occurs in the microcirculation. We found that intra-arterial administration of the calcium antagonist Nitrendipine greatly inhibited the vasoconstriction induced by cocaine in all three arteriole orders. The degree of inhibition ranged from 44 to 56%. Combined administration of benzodiazepine and an angiotensin converting enzyme inhibitor has also been reported to protect rats against cocaine-induced hypertension and to increase survival rates after a toxic dose of cocaine. Since the mechanisms of this protection are not yet clear, we also studied the effect of the angiotensin converting enzyme inhibitor Enalaprilat on cocaine-induced vasoconstriction. Intra-arterial administration of Enalaprilat inhibited this vasoconstriction slightly but significantly in arteriole orders 2 and 3 by 27 and 24% respectively, but not in order 4. We concluded that Nitrendipine is a powerful inhibitor of cocaine-induced vasoconstriction in the microcirculation. The small but significant inhibition found with Enalaprilat for the larger arterioles suggests that the local angiotensin II level may affect the response to cocaine. However, since the Enalaprilat-induced inhibition was very limited, we conclude that mechanisms other than those occurring in the peripheral microcirculation account for the protection afforded by Enalaprilat against the harmful effects of cocaine.
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PMID:Microvascular effects of cocaine; interaction with nitrendipine and enalaprilat. 164 95

In order to investigate renin- and angiotensin-independent mechanisms of the angiotensin converting enzyme (ACE) inhibitor ramipril we examined the effects of ramiprilat on calcium mobilization in cultured vascular smooth muscle cells. Ramiprilat (10(-7) M) induced a slow increase of basal [Ca2+]i from 52 +/- 7 nM to 162 +/- 12 nM (p less than .001). This increase of basal [Ca2+]i was associated with contraction of vascular smooth muscle cells as assessed by microscopy in vitro. While ramiprilat itself induced an increase of basal [Ca2+]i, the Ca(2+)-mobilizing effect of angiotensin II (AII) was blunted in the presence of the ACE inhibitor (659 +/- 38 nM vs 360 +/- 45 nM, p less than .001). The calcium channel blocker verapamil did not affect the stimulatory effect of ramiprilat on basal [Ca2+]i. The intracellular Ca2+ antagonist TMB 8 attenuated the ramiprilat-induced increase of basal [Ca2+]i (162 +/- 12 nM vs 101 +/- 14 nM, p less than .05). In the present study, the effect of ramiprilat on [Ca2+]i was not blocked by inhibition of prostaglandin synthesis by meclofenamate (10(-5) M); however, this finding does not rule out in vivo effects of ramiprilat-stimulated prostaglandins. These results suggest that ramipril affects Ca2+ kinetics in vascular smooth muscle cells. Ramiprilat-induced contraction of cultured smooth muscle cells may not be relevant in vivo, but the increase of basal [Ca2+]i by ramiprilat may reflect a "reset" of the cellular Ca(2+)-mobilizing mechanism or a depletion of cellular Ca2+ stores and may thus explain the attenuation of the Ca(2+)-mobilizing effect of AII. This mechanism may result in a decrease of vasopressor-dependent vascular tone in vivo and may contribute to the vasodilatory effect of ramipril.
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PMID:[Effects of the angiotensin converting enzyme inhibitor ramipril on calcium (Ca2+) kinetics in smooth muscle cells]. 165 Aug 62


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