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

Chronic cor pulmonale is defined as right heart hypertrophy or right ventricular dilatation and/or chronic right heart failure. There are many etiologies which largely determine mortality and drug therapy, but the common cause is increased right ventricular work from primary or secondary pulmonary hypertension assuming two prototypes, the asphyxial and the vascular obliterative type. The main focus of this review concentrates on the various drugs to reduce pulmonary vascular pressure and resistance. The value to correct hypoxaemia is mentioned with regard to its demonstrated important effect of asthmatic patients with cor pulmonale. Continuous oxygen therapy and a potential therapy by almitrine, a respiratory stimulant, have been suggested. Phosphodiesterase inhibitors and dopaminergic drugs have been used successfully to improve right cardiac function in a small number of patients. The use of prostacyclin has a large potential to effectively correct pulmonary vascular haemodynamics but its use is fairly limited by the need of continuous intravenous application. New oral drugs under investigation which stimulate endogenous prostacyclin as well as thromboxane synthetase inhibitors still need further evaluation but might be of potential benefit. The comparison of the side-effects due to vasodilators and calcium antagonists argues for the use of calcium channel blockade for patients with pulmonary hypertension. To define the role of angiotensin converting enzyme inhibitors or the more recently introduced potassium channel openers for treatment of chronic cor pulmonale still await detailed, controlled studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The drug therapy of chronic cor pulmonale]. 186 13

1. Cardiac failure is a clinical syndrome of symptoms and signs, which can be confirmed by imaging or invasive haemodynamic techniques. It may be caused by systolic or diastolic dysfunction, but systolic dysfunction rarely occurs alone. It is important to ascertain the degree to which each contributes, and the precise aetiology of the condition, particularly in relation to surgically correctable lesions. 2. Non-pharmacological approaches including weight loss, salt restriction and lifestyle changes may be beneficial in some patients, and diuretics, which reduce the load on the heart, are the traditional baseline therapy. 3. Digitalis has been used where problems with contractility predominate, but its beneficial effect has been disputed, and expectations of improvement in patients in sinus rhythm should not be too high. 4. Vasodilators have been considered as the next line of treatment. Arteriolar dilators tend to increase cardiac output, but have little effect on pulmonary artery wedge pressure, and venodilators tend to have the opposite effect. Probably both actions are necessary and angiotensin converting enzyme (ACE) inhibitors, which have both, have proved effective in terms of symptoms and survival. 5. Various other inotropic agents have been tried. Phosphodiesterase inhibitors improve exercise tolerance, but may increase the probability of serious arrhythmias, already a significant cause of sudden death. beta 1-partial adrenoceptor agonists such as xamoterol have shown some promise, and anti-arrhythmic therapy has also been considered. 6. Drugs which prevent progression of myocardial damage would prove a great advance, and beta-adrenoceptor antagonists and calcium channel blockers appear to have considerable potential in this area.
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PMID:Treatment of congestive heart failure--state of the art and future trends. 257 53

New agents for treating chronic heart failure include angiotensin converting enzyme (ACE) inhibitors, betablockers and phosphodiesterase inhibitors. The ACE inhibitors represent the major therapeutic advance of the 1980-1990 decade. This is the most effective class of drugs on survival, whatever the stage of heart failure and it shows the evolution towards symptoms in asymptomatic patients. Studies currently under way are evaluating the dose-effect relationship of ACE inhibitors. Betablockers improve the quality of life and physical performance but a benefit on mortality has not been shown in two recent trials. Phosphodiesterase inhibitors improve quality of life and physical performance at the price of an increase in mortality. Therefore, they are not indicated in the treatment of heart failure. However, new molecules such as vesnarininone or pimobendan are under trial. Finally, in the next few years, the introduction of antagonists to Angiotensin II receptors is eagerly awaited.
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PMID:[Treatment of chronic heart failure: current views]. 748 9

The analysis of currently used therapeutic targets provides considerable input in the choice of current and future therapies for dilated cardiomyopathy and congestive heart failure. Of the ion flux agents, a definitive answer concerning digoxin will soon be available. Currently, digoxin is likely of benefit to patients with persistent heart failure and significantly enlarged hearts despite therapy with preload and afterload reducing agents. Most currently available calcium channel blocking agents do not appear to be effective, although newer agents such as amlodipine and felodipine have yet to be adequately tested. Vesnarinone, which operates through the sodium and potassium rectifying channels and has limited phosphodiesterase inhibition, appears to provide a significant improvement in mortality and in symptoms. Part of the latter effect may be due to its anticytokine properties, which are currently being investigated. Analysis of vascular endothelial agents indicate that not all of the vasoactive agents improve survival, as demonstrated with prazosin and flosequinan. The dose of agents may be important, again demonstrating that less is better. Finally, those with additional effects, such as inositol triphosphate stimulation, may offer additional unique properties that may, in the future, provide benefit. Phosphodiesterase inhibitors are potentially beneficial in the short term but clearly should be avoided for long-term use. Lower doses of these agents are now being investigated, but the weight of evidence is against agents that operate primarily through phosphodiesterase inhibition. Renin angiotensin agents are the most efficacious of therapies available at this time. New angiotensin converting enzyme inhibitors are likely to add little to what is already known.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New medical therapies for advanced left ventricular dysfunction. 779 29

Recent analyses suggest that about 67-68% of men with hypertension have some degree of erectile dysfunction (ED). With about 25 million men in the US with hypertension, substantial numbers of hypertension-related ED exist that tend to be of a more severe nature than the general population. Men with ED are also more likely to have hypertension. Thiazide diuretic and beta-blocker therapy may contribute to ED. Phosphodiesterase-5 (PDE5) inhibitors are effective therapy in men with ED owing to hypertension who are taking antihypertensive medicines including those on multiple antihypertensive medicines. The addition of PDE5 inhibitors to usual common antihypertensive medicines (diuretics, beta blockers, calcium blockers, angiotensin converting enzyme inhibitors and angiotensin receptor blockers) results in either no or small additive reductions in blood pressure (BP) and no increase in serious clinical adverse events. There are however precautions regarding the use of PDE5 inhibitors in patients taking alpha blockers for either hypertension or benign prostatic hypertrophy, as some patients may develop orthostatic hypotension. Organic nitrates remain an absolute contraindication for PDE5 inhibitors because synergistic and symptomatic reductions in BP may occur in some patients with this drug combination.
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PMID:Erectile dysfunction and hypertension. 1715 96

Regulation of the peripheral vascular resistance via modulating the vessel diameter has been considered as a main determinant of the arterial blood pressure. Phosphodiesterase enzymes (PDE1-11) hydrolyse cyclic nucleotides, which are key players controlling the vessel diameter and, thus, peripheral resistance. Here, we have tested and reported the effects of a novel selective PDE1 inhibitor (BTTQ) on the cardiovascular system. Normal Sprague Dawley, spontaneously hypertensive (SHR), and Dahl salt-sensitive rats were used to test in vivo the efficacy of the compound. Phosphodiesterase radiometric enzyme assay revealed that BTTQ inhibited all three isoforms of PDE1 in nanomolar concentration, while micromolar concentrations were needed to induce effective inhibition for other PDEs. The myography study conducted on mesenteric arteries revealed a potent vasodilatory effect of the drug, which was confirmed in vivo by an increase in the blood flow in the rat ear arteriols reflected by the rise in the temperature. Furthermore, BTTQ proved a high efficacy in lowering the blood pressure about 9, 36, and 24 mmHg in normal Sprague Dawley, SHR and, Dahl salt-sensitive rats, respectively, compared to the vehicle-treated group. Moreover, additional blood pressure lowering of about 22 mmHg could be achieved when BTTQ was administered on top of ACE inhibitor lisinopril, a current standard of care in the treatment of hypertension. Therefore, PDE1 inhibition induced efficient vasodilation that was accompanied by a significant reduction of blood pressure in different hypertensive rat models. Administration of BTTQ was also associated with increased heart rate in both models of hypertension as well as in the normotensive rats. Thus, PDE1 appears to be an attractive therapeutic target for the treatment of resistant hypertension, while tachycardia needs to be addressed by further compound structural optimization.
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PMID:Selective Phosphodiesterase 1 Inhibitor BTTQ Reduces Blood Pressure in Spontaneously Hypertensive and Dahl Salt Sensitive Rats: Role of Peripheral Vasodilation. 3301 77