Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Eight hypertensive patients with angina pectoris had placebo added to their existing medications for 8 weeks, then incremental doses of active labetalol with simultaneous stepwise reduction in other medicines until blood pressure was satisfactorily controlled; after that only labetalol and thiazide (8 weeks) and finally labetalol-placebo together with previous beta-adrenoreceptor antagonists and thiazide for 4 weeks were administered. 2. During the labetalol plus thiazide period resting blood pressures and measurements obtained during isotonic exercise, isometric exercise and the cold pressor test were significantly lower than during the initial placebo addition period. Angina scores were significantly reduced during this period. 3. During the final treatment with placebo, beta-adrenoreceptor antagonist and thiazide, blood pressures remained reduced, but angina was significantly worse. 4. Labetalol which antagonizes both alpha- and beta-adrenoreceptors produced better relief of angina pectoris than beta-adrenoreceptor antagonists during improvement in blood pressure in hypertensive patients.
Clin Sci Mol Med Suppl 1978 Dec
PMID:Labetalol in hypertensive patients with angina pectoris: beneficial effect of combined alpha- and beta-adrenoreceptor blockade. 3 6

1. A study was conducted amongst 1247 treated hypertensive patients to determine the predictive power of untreated baseline and achieved treated blood pressures in the development of the complications of hypertension. In addition the relative importance of systolic and diastolic pressures was calculated. 2. Statistical analysis was done by calculating univariate differences in blood pressure between cases with and without complications. The higher the univariate distance, the greater the predictive power. 3. Blood pressures achieved during treatment were more important than baseline pressures for predicting stroke in both men and women, confirming the benefits of antihypertensive therapy in preventing strokes. 4. There was some evidence of prevention of myocardial infarction in men and of angina in women as a result of therapy. 5. There was no evidence to suggest that any one group of drugs, including beta-adrenoreceptor-blocking drugs and thiazides, conferred any extra benefit in preventing coronary heart disease. 6. The systolic blood pressures achieved during treatment predicted stroke better than diastolic pressure, but no consistent trends were found for coronary heart disease.
Clin Sci Mol Med Suppl 1978 Dec
PMID:Relation between prognosis and the blood pressure before and during treatment of hypertensive patients. 3 9

Cardiac extraction, oxidation and release of plasma free fatty acids (FFA) was measured by coronary sinus catheterization, utilizing infusions of 3H palmitate and 14C oleate, in patients with ischaemic heart disease (IHD) at rest and during pacing induced angina pectoris and, for comparison, in healthy men of similar and younger age and men with hypertriglyceridaemia (HTG). At rest IHD patients differed from healthy men only by greater cardiac fatty acid release, which correlated with a significant glycerol release. In IHD patients, unlike in healthy men, myocardial extraction of both palmitate and oleate decreased while fractional oxidation of oleate increased during pacing. Fatty acid release was unaltered. Men with HTG had at rest higher myocardial FFA extraction than IHD patients, which did not decrease during pacing, but like in the patients oleate fractional oxidation increased on pacing. It is concluded that, in the moderately ischaemic human heart, the restricted blood flow may contribute to limit the fatty acid flux into the myocardium. The augmented cardiac fatty acid release in IHD patients is not related to ischaemia per se but may derive from an increased amount of cardiac interstitial fat.
Mol Cell Biochem
PMID:Fatty acid turnover in the ischaemic compared to the non-ischaemic human heart. 277 38

Circulatory blood corpuscles have enzymes catalyzing arachidonic acid. Platelets have cyclo-oxygenase system which produce highly vasoconstrictive and thrombogenic thromboxane A2 (TXA2). Neutrophils have another type of arachidonate metabolism system, lipoxygenase enzymes, which produce hydroxyeicosatetraenoic acids (HETE) and leukotrienes (LT), mediating inflammatory reactions. These arachidonate metabolites were found to play important roles in the evolution of myocardial ischemia. Thromboxane B2 (TXB2) a stable metabolite of TXA2, was elevated in peripheral blood of patients with angina pectoris. This elevation of TXB2 was supposed to be derived from platelet activation in coronary circulation due to altered production of TXA2 and prostacyclin (PGI2). Augmentation of TXA2 was also observed in patients with acute myocardial infarction. TXA2 synthetase inhibitors decreased plasma levels of TXB2 in these patients accompanied by attenuation of infarct size. Neutrophils were found to accumulate in ischemic myocardium and were augmented at reperfusion phase especially at interface between infarcted and risk zone. These infiltrated neutrophils may also provide deleterious effects on myocardial cells by producing lipoxygenase metabolites. In fact, a chemotactic and vasoconstrictive lipoxygenase product, 12-HETE, was produced selectively in ischemic myocardial tissue of an occlusion-reperfusion model. During evolution of myocardial cell damage, platelets and neutrophils, accumulated in ischemic tissue, may contribute to the exacerbation of microcirculatory disorders by producing vasoactive prostanoids, leading to expansion of myocardial necrosis. We should gain insights into these cellular interactions through arachidonate metabolism under normal and catastrophic conditions of coronary circulation.
J Mol Cell Cardiol 1988 Mar
PMID:Arachidonate metabolism in myocardial ischemia and reperfusion. 313 47

The ability of the beta-receptor antagonist propranolol to influence the response of isolated cardiac and vascular smooth muscle to several classes of calcium channel blockers was examined. For comparison, the interactions between propranolol and other classes of negative inotropic and vasorelaxant agents was also evaluated. The results of these studies demonstrate that propranolol pre-treatment significantly enhances the in vitro response to the dihydropyridine calcium channel blocker nifedipine, but not the thiazapine calcium channel blocker diltiazem. This enhancement was unrelated to the negative inotropic or vasorelaxant properties of these agents. In addition, propranolol pre-treatment of rat cortical membranes also enhanced the affinity of nifedipine for the 3H-nitrendipine binding site, but did not alter the effect of diltiazem on 3H-nitrendipine binding. These observations suggest that a direct interaction may exist between beta-receptor antagonists and dihydropyrine-type calcium channel blockers. This interaction may be an important factor in selecting drug therapy for conditions such as hypertension and angina.
J Mol Cell Cardiol 1988 Oct
PMID:Interaction between propranolol and calcium channel blockers in cardiac and vascular smooth muscle. 321

The clinical use of calcium antagonist drugs in coronary artery disease preceded knowledge of the mechanism of their action. Basic research into their pharmacological actions and development of a wide range of compounds which block calcium entry into cells enabled clinicians to greatly expand the indications for their use. Thus the calcium antagonists were rediscovered and found to be potent anti-anginal drugs when used in adequate dosage for effort related angina. Knowledge of their potent relaxing action on vascular smooth muscle led to their use in coronary artery spasm. The exact trigger mechanism/s for spasm and the reason for enhanced vascular reactivity remain unclear, perhaps explaining the failure of specific antagonist therapy. Calcium antagonists acting nonspecifically inhibit both induced and spontaneous attacks of vasospastic angina. They may favourably influence the prognosis and are now drugs of first choice for this condition. The vasodilator action of these drugs has most recently been utilized to treat hypertension, with efficacy confirmed in many controlled trials. Unlike other vasodilators, the calcium antagonists reduce blood pressure without salt and water retention, and with mild or no stimulation of renin, aldosterone, or sympathetic nervous overactivity, and without postural effects. This spectrum of action makes them ideal therapeutic agents, and current guidelines are changing to include calcium antagonists as first or second line therapy.
J Mol Cell Cardiol 1987 May
PMID:Calcium antagonist drugs in the treatment of coronary spasm, effort angina and hypertension. 330 67

In patients with hypertrophic cardiomyopathy, clinical symptoms such as exertional dyspnea, angina and collapse are considered to be rather the consequence of diastolic than of systolic dysfunction of the left ventricle. Beta-blocker therapy is aimed at reducing systolic overcontraction while calcium blockers predominantly therapy is aimed at reducing systolic overcontraction while calcium blockers predominantly improve diastolic filling characteristics. Therefore 61 consecutive patients with well defined hypertrophic cardiomyopathy were treated with calcium channel blockers: 60 patients with verapamil at average dose 530 mg (320 to 720 mg/d) and one patient received 30 mg nifedipine. All patients had clinical, noninvasive and cardiac catheterization evaluation at the time of entry into the study. Therapy was continued for an average of 54 months (10 to 96). Follow-up studies were performed at 6-month intervals. Subjective improvement was achieved in 47 of 55 symptomatic patients (85%). Heart size, judged as heart volume from tele-chest X-ray in supine position, showed a reduction in 36/61, no change in 15/61 and increase in 10/61. On average in all 61 patients, a significant reduction from 947 to 833 ml/1.73 m2 was seen. Twenty-six patients who had been followed for an average of 24 months prior to verapamil therapy on beta blockers or no treatment had heart volume increases averaging 12% in the pre-verapamil period. Electrocardiography (ECG) showed a significant reduction in QRS amplitude and a tendency towards normalization of ST/T segments. Serial echocardiography study showed small but significant reduction in left atrial diameter. Repeat catheterization was performed in 19 patients and a significant reduction in intraventricular pressure gradient, left ventricular muscle mass and coronary artery diameter was demonstrated. Three patients died during the study (256 patient-treatment-years) for an annual mortality rate of 1.3%. This mortality is considerably lower than reported for patients receiving no treatment, beta-blockade, or surgery. Of all 61 patients only one had surgery related to the hypertrophic cardiomyopathy. One patient had the dose of verapamil reduced because of the occurrence of heart block. No patient discontinued the drug because of side-effects. Utilizing serial noninvasive and invasive studies, we conclude that verapamil therapy in hypertrophic cardiomyopathy results in objective and subjective improvement, a low death rate and little need for operation as compared to standard therapy.
J Mol Cell Cardiol 1985 Jul
PMID:Treatment of hypertrophic cardiomyopathy: relation to pathological mechanisms. 404 Sep 78

We used Western blot, a highly sensitive technique that detects amounts of protein as low as 0.1 to 1.0 ng, to investigate the possible presence in the blood stream of the contractile protein alpha-actin in 29 patients diagnosed with angina pectoris (Braunwald's classification). Circulating protein was identified with a monoclonal antibody specific for cardiac alpha-actin. Of the 20 control samples of blood, the immunoblot results were negative for alpha-actin in 19. Of the 30 patients with skeletal muscle damage caused by surgery, 27 were negative for circulating alpha-actin. Of the 29 patients with angina pectoris, circulating alpha-actin was found in 19 as a 43 kDa band in immunoblots. Of the four patients with anterior acute myocardial infarction, mean concentration of circulating alpha-actin was 58 mg/l. Among the patients with angina pectoris, the highest circulating concentrations (mean 40 mg/l) was found in those with prolonged angina (class III B, according to Braunwald's classification). In the entire group of individuals with angina pectoris alpha-actin was detectable in serum for up to 175 h after the onset of pain, and showed two peaks, one at 1 h (112 mg/l) and one at 50 h (82 mg/l) after the onset of pain. These findings reinforce the notion that unstable angina should be considered a serious condition.
J Mol Cell Cardiol 1993 Jan
PMID:Circulating alpha-actin in angina pectoris. 844 Nov 77

Within a few seconds after a sudden reduction of coronary blood flow regional contractile dysfunction ensues. The mechanisms responsible for the rapid reduction in contractile function during acute myocardial ischemia remain unclear, but may involve a rise in inorganic phosphate. When severe ischemia, such as resulting from a sudden and complete coronary artery occlusion, is prolonged for more than 20-40 min, myocardial infarction develops, and there is irreversible loss of contractile function. When myocardial ischemia is less severe but nevertheless prolonged, the myocardium is dysfunctional but can remain viable. In such ischemic and dysfunctional myocardium, contractile function is reduced in proportion to the reduction in regional myocardial blood flow; i.e. a state of "perfusion-contraction matching" exists. The metabolic status of such myocardium improves over the first few hours, as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. Ischemic myocardium, characterized by perfusion-contraction matching, metabolic recovery and lack of necrosis, has been termed "short-term hibernating myocardium". Short-term hibernating myocardium can respond to an inotropic stimulation with increased contractile function, however, at the expense of a renewed worsening of the metabolic status. This situation of an increased regional contractile function at the expense of metabolic recovery during inotropic stimulation can be used to identify short-term hibernating myocardium. When inotropic stimulation is prolonged, the development of short-term hibernation is impaired and myocardial infarction develops. The mechanisms responsible for the development of short-term myocardial hibernation remain unclear at present; a significant involvement of adenosine and of activation of ATP-dependent potassium channels has been excluded. Whereas short-term hibernation is well characterized in animal experiments, the existence of hibernation over weeks or months (long-term hibernation) can only be inferred from clinical studies. Hibernation, as defined by Rahimtoola, is a state of chronic contractile dysfunction which is fully reversible upon reperfusion. Clinical syndromes consistent with the existence of myocardial hibernation include unstable and stable angina, acute myocardial infarction and left ventricular dysfunction and/or congestive heart failure. In long-term hibernating myocardium morphological alterations occur; the myofibrils are reduced in number and disorganized and myocardial glycogen content as well as the extracellular collagen network are increased. Thus, despite the fact that the myocardium remains viable during persistent ischemia and contractile dysfunction is reversible upon reperfusion, there are severe morphological alterations. Understandably, full functional recovery following reperfusion might therefore require weeks or even months.
J Mol Cell Cardiol 1996 Dec
PMID:Hibernating myocardium: a review. 900 53

Atherosclerosis and hypercholesterolaemia disturb the endothelium-dependent regulation of the vascular tone by the labile liposoluble radical nitric oxide. This defect predisposes to vasospasm and ischaemia, with anginal pain as a clinical manifestation. It is now appreciated that endothelial dysfunction is an early event in atherogenesis, possibly also involving the microcirculation, in which atherosclerosis does not develop. Furthermore, it is becoming clear that nitric oxide, in addition to regulating vasomotion, might also modulate the progression of the disease process. The latter notion could have therapeutic implications.
Mol Med Today 1996 Dec
PMID:Nitric oxide and atherosclerosis: possible implications for therapy. 901 92


1 2 3 4 5 6 7 8 9 10 Next >>