Drugs online research references
medizin.uni-koeln.de
OBJECTIVE: beta-Blockers improve cardiac function and survival in heart failure patients. The underlying mechanisms are not completely elucidated. Differences between agents might be important for the development of more specific therapeutical approaches. This study investigated whether metoprolol or carvedilol alter beta-adrenergic signaling differently. METHODS: beta-Adrenoceptor density and systolic function were determined in rat adult ventricular cardiac myocytes. RESULTS: 12 h isoprenaline-treatment (Iso, 1 micromol/l) reduced beta-adrenoceptor density by 33% (P<0.01). The effect was abolished by incubation with isoprenaline plus metoprolol (3 micromol/l), but was more pronounced after coincubation with carvedilol (0.003 micromol/l, P<0.05 Carv vs. Iso). Metoprolol alone had no effect on beta-adrenoceptor density, but carvedilol induced a decrease in receptor density even in absence of isoprenaline (P<0.05 Carv vs. ctr.). The isoprenaline (0.0003-10 micromol/l) induced concentration-dependent increase in myocyte shortening was blunted after 12 h preincubation with Iso (1 micromol/l, P<0.001). This reduction was abolished or partly prevented by coincubation with metoprolol or carvedilol, respectively. Carvedilol decreased the number of receptors which had to be occupied by isoprenaline in order to obtain 50% and 90% increase in myocyte cell shortening. Comparison of guanine nucleotide-dependent binding characteristics of isoprenaline, carvedilol and metoprolol revealed beta-receptor agonist like binding characteristics for carvedilol, but antagonist like binding characteristics for metoprolol. CONCLUSION: Metoprolol but not carvedilol prevents isoprenaline-induced downregulation of myocyte beta-adrenoceptors. The difference might be due to specific binding properties of the beta-blockers. Restoration of isoprenaline responsiveness by carvedilol might be due to improved coupling of beta-receptors to postreceptor effects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11164847&dopt=Abstract
J Intern Med. 1989 Mar;225(3):165-72.
The relationship between casual and ambulatory blood pressure in essential hypertension: the influence of work, duration of hypertension and antihypertensive treatment.
Eiskjaer H, Pedersen EB.
Department of Medicine C, Aarhus Kommunehospital, Denmark.
Casual blood pressure (BP) and ambulatory BP (mean 24-h BP) were determined in 23 untreated patients with essential hypertension and in 11 normotensive healthy control subjects. Mean 24-h BP was significantly lower than casual BP in patients with essential hypertension, but not in control subjects. This was demonstrated in the patients who did not work during the ambulatory BP monitoring and in the patients with newly recognized hypertension, whereas no differences were revealed either in the patients who went to work or had a known duration of hypertension longer than 6 months. The size of the difference between casual BP and mean 24-h BP was unaffected by antihypertensive therapy with metoprolol and also individually reproducible. An accordance between casual and ambulatory BP measurements in evaluation of the efficacy of antihypertensive treatment was found in 75% of the patients. Casual BP and mean 24-h BP were weakly correlated both before and during antihypertensive treatment. It is concluded that the higher casual BP than ambulatory BP in essential hypertension may be a specific characteristic of the disease. Both work and known duration of hypertension longer than 6 months eliminate the difference between casual ambulatory BP in essential hypertension. Ambulatory BP monitoring seems to be superior to casual BP measurements in the evaluation of antihypertensive treatment.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2703798&dopt=Abstract
uiowa.edu
BACKGROUND: Long-term metoprolol therapy improves cardiac performance and decreases mortality in patients with chronic congestive heart failure (CHF). This study examined the effect of long-term metoprolol therapy on renal sodium handling in an experimental rat model of CHF. METHODS AND RESULTS: Rats with left coronary ligation and myocardial infarction-induced CHF were treated with metoprolol (1.5 mg. kg-1. h-1) or vehicle for 3 weeks by osmotic minipump. They were then evaluated for their ability to excrete a short-term sodium load (5% body weight isotonic saline infusion over 30 minutes) and a long-term sodium load (change from low- to high-sodium diet over 8 days). All CHF rats had left ventricular end-diastolic pressure >10 mm Hg, and heart weight/body weight ratios averaged 0.68+/-0.02% (versus control of approximately 0.40%). Compared with vehicle CHF rats (n=19), metoprolol CHF rats (n=18) had lower basal values of mean arterial pressure (122+/-3 versus 112+/-3 mm Hg) and heart rate (373+/-14 versus 315+/-9 bpm) and decreased heart rate responses to intravenous doses of isoproterenol. During short-term isotonic saline volume loading, metoprolol CHF rats excreted 54+/-4% more of the sodium load than vehicle CHF rats. During long-term dietary sodium loading, metoprolol CHF rats retained 28+/-3% less sodium than vehicle CHF rats. CONCLUSIONS: Metoprolol treatment of rats with CHF results in an improved ability to excrete both short- and long-term sodium loads.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10393685&dopt=Abstract
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