Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In six patients with hypertriglyceridaemia presenting whilst receiving treatment with beta-adrenoreceptor blocking drugs (mean serum triglycerides 31.2 mmol/l) the half-life (t1/2) of an intravenously administered triglyceride emulsion was 32.8 +/- 7.9 min (mean +/- SEM) on beta-blocker and 22.8 +/- 4.8 min after stopping beta-blocker treatment. In three of these patients subsequent administration of a beta-blocker with intrinsic sympathomimetic activity had no effect on t1/2. In a cross-over trial of placebo, atenolol (beta 1-blocker), propranolol (beta 1- and beta 2-blocker) and pindolol (beta 1- and beta 2-blocker with intrinsic sympathomimetic activity) in 11 normal men t1/2 was 11.8 +/- 0.9, 12.6 +/- 1.1, 14.3 +/- 1.7 and 12.4 +/- 1.1 min respectively. None of the apparent differences achieved statistical significance, but in two men marked increases in t1/2 occurred on propranolol. The concentrations of serum triglycerides and very low density lipoprotein cholesterol in the normal men were, however, increased by beta-blockade, most markedly by pindolol. Serum high density lipoprotein (HDL) cholesterol concentration decreased in normal men on beta-blockers, most clearly on atenolol and propranolol. This decrease was due to a reduction in cholesterol in the HDL2 subfraction. No statistically significant effects on serum low density lipoprotein cholesterol or apolipoprotein B concentrations occurred in the normal men. The doses of atenolol and propranolol used in this study were equipotent as judged by the heart rate response to exercise.
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PMID:Short-term effects of beta-adrenoceptor blocking drugs with and without cardioselectivity and intrinsic sympathomimetic activity on lipoprotein metabolism in hypertriglyceridaemic patients and in normal men. 286 62

Isolated kidney-cortical tubule suspensions and microdissected nephron segments from fed rats were used to study the action of catecholamines on gluconeogenesis. Gluconeogenesis from rat tubule suspension incubated with 5 mM pyruvate was stimulated maximally by 10(-5) M methoxamine, an alpha 1-selective agonist, and 10(-6) M noradrenaline by 29.2 +/- 5.2% (mean +/- SEM) and 32.6 +/- 2.9%, respectively. These effects were completely inhibited by 10(-7) M prazosin, a beta 1-selective antagonist. Yohimbine, an alpha 2-antagonist, also inhibited the effect, but only at a higher concentration (5 X 10(-5) M). Gluconeogenesis was not stimulated by isoproterenol, a alpha-agonist, at any concentrations between 10(-5) and 10(-7) M. With microdissected nephron segments, only the proximal tubule possessed gluconeogenic activity. Within the proximal tubule, the proximal convoluted tubule (PCT) revealed higher gluconeogenic activity than the proximal straight tubule (PST). Methoxamine at 10(-5) M stimulated gluconeogenesis in PCT, whereas in PST no increase of gluconeogenesis was observed. From these results, it can be concluded that an alpha 1-adrenergic agonist specifically stimulates renal gluconeogenesis in PCT, but not in PST.
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PMID:Evidence that alpha-1-adrenergic stimuli specifically increase gluconeogenesis of the isolated proximal convoluted tubule in the rat. 287 97

The number of beta-adrenoceptors and their affinity for the radioligand 125I-labelled cyanopindolol (125I-CYP) were measured in crude membrane preparations of left ventricle, spleen and lung from Wistar rats exposed to 28 days continuous hypoxia. beta-Adrenoceptor density in the left ventricle was not significantly altered after exposure to chronic hypoxia (binding site maxima, Bmax.: normoxic control 36 SEM 5, hypoxic 24.8 SEM 2 fmol/mg of protein). There was no change in beta-adrenoceptor number in the spleen in response to chronic hypoxia (Bmax.: normoxic control 76 SEM 19 fmol/mg of protein, hypoxic 80 SEM 15 fmol/mg of protein). Chronic hypoxia resulted in a significant increase in beta-adrenoceptor number in lung tissue (binding site maxima, Bmax.: normoxic control 406 (SEM 31) fmol/mg of protein; hypoxic 535 (SEM 30) fmol/mg of protein, P less than 0.01 without change in the dissociation constant (KD) of the radioligand. beta-Adrenoceptor subtypes in lung homogenates were studied by establishing displacement curves for 125I-CYP by ICI 118551 (a selective beta 2-antagonist). A significant difference was seen in the proportion of beta 1-/beta 2-adrenoceptor subtypes after hypoxia (normoxic control 66 SEM 2.5%, hypoxic 79 SEM 2.4% beta 2-adrenoceptors, P less than 0.01). alpha 1-Adrenoceptor number in lung membranes was measured with 125I-labelled 2-[beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone (125I-HEAT). No difference was seen in the number of alpha 1-receptors in normoxia and in chronic hypoxia [Bmax.: normoxic control 48 (SEM 3), hypoxic 48 (SEM 5) fmol/mg of protein].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue specific modulation of beta-adrenoceptor number in rats with chronic hypoxia with an attenuated response to down-regulation by salbutamol. 300 74

Development of appropriate clinical dose regimens of individual plasminogen activators such as tissue-type plasminogen activator (t-PA) has generally relied primarily on nonpharmacological endpoints such as angiographically documented clot lysis. The recent availability of monoclonal antibodies that differentiate products of plasmin lysis of fibrin from those of lysis of fibrinogen should permit delineation of the relative fibrin specificity of different plasminogen activators or of different doses of the same activator in vivo. Thus, their use should accelerate and facilitate development of implementation of optimal dose regimens for diverse activators and combinations of activators. The present study was designed to determine whether assay of such markers effectively differentiates effects of two doses of t-PA, each of which are comparably effective in opening infarct-related arteries, in patients studied at the Washington University Clinical Unit of the National Institutes of Health-sponsored Thrombolysis in Myocardial Infarction Trial. The extent of lysis of fibrin and of lysis of fibrinogen by plasmin resulting from administration of t-PA was evaluated in 19 patients given 150 mg t-PA over 6 hours and 17 given 100 mg over the same interval by assay of serially obtained plasma samples for crosslinked fibrin degradation products (XL-FDP) and B beta 1-42, a peptide released when fibrinogen is degraded to fragment X by plasmin. XL-FDP were markedly elevated after 6-hour infusions of both doses of t-PA. However, elevations were not more with the higher dose [peak value, 4,321 +/- 986 ng/ml (+/- SEM)] compared with the lower dose (3,397 +/- 1,096 ng/ml) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization in vivo of the fibrin specificity of activators of the fibrinolytic system. 313 54

The effect of metoprolol, a beta 1-blocker, on atherogenesis was evaluated in rabbits fed a diet supplemented with 0.25% cholesterol and 3% coconut oil for 21 weeks. After 7 weeks on the diet, the rabbits were randomly divided into treated (n = 22) and untreated (n = 22) groups. Treated animals received metoprolol subcutaneously by an osmotic pump for 14 weeks, resulting in a plasma level of 774 +/- 69 nM during the investigation. Plasma concentrations of cholesterol, triglycerides, and phospholipids did not differ between the two groups. Nor were there any significant differences between the two groups in plasma concentrations of apolipoprotein A-I, apolipoprotein B, apolipoprotein C-III, and apolipoprotein E measured by electroimmunoassay. At the end of the study, the aortas were cut into three portions and the extent of atherosclerosis was determined by morphometry. The group that had received metoprolol had significantly (p less than 0.015) less atherosclerosis in the aorta (ascending plus arch 37.8 +/- 6.8%, thoracic 32.9 +/- 6.1%, abdominal 19.8 +/- 6.1% of total intimal area; mean +/- SEM) than the controls (ascending plus arch 54.9 +/- 7.1%, thoracic 48.0 +/- 6.2%, abdominal 25.9 +/- 5.5%).
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PMID:Effect of metoprolol on diet-induced atherosclerosis in rabbits. 334 91

Effects of propranolol and metoprolol on sigmoid colonic motility were studied in 12 healthy volunteers in a double-blind randomized fashion. Colonic pressure was recorded 15-18 cm from anus and contractile activity quantified for periods of 25 min. On separate days propranolol, metoprolol, and placebo, respectively, was administered intravenously preceded by a control period. After propranolol, 10 mg intravenously, pressure activity increased significantly from 3.8 +/- 1.1 (SEM) kPa X min (28 +/- 8 mm Hg X min) to 5.9 +/- 1.0 kPa X min (44 +/- 8 mm Hg X min) (P less than 0.001). Also, after propranolol, 5 mg intravenously, the pressure activity was increased (P less than 0.05). After metoprolol, 10 mg intravenously, contractile activity increased from 4.3 +/- 0.9 kPa X min (32 +/- 7 mm Hg X min) to 6.1 +/- 1.0 kPa X min (46 +/- 8 mm Hg X min) (P less than 0.01). The two drugs caused equipotent reduction of heart rate. After placebo, no effect on sigmoid pressure or heart rate was observed. The study shows that unselective (propranolol) and beta 1-selective (metoprolol) beta-blocking drugs enhance distal colonic pressure in man. Colonic motility seems to be under sympathetic beta-adrenergic influence even under fairly unstrained conditions.
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PMID:Effects of beta-adrenoceptor blocking drugs on human sigmoid colonic motility. 613 4

Although right ventricular function may be examined by following the passage (first pass) of a bolus of radionuclide through the right heart before it reaches the left heart, the counts detected with conventional gamma cameras in such a short time interval are low; moreover, repeated determinations would result in an unacceptable radiation burden to the patient. We have modified the gated equilibrium blood pool method to allow repeated assessment of the right ventricular ejection fraction (RVEF) and have compared the results with the first-pass method in 43 patients. Good agreement was obtained between the two methods (r = 0.91, p less than 0.001). The mean difference between the two methods was 0.04 with an intra-observer variation for the equilibrium studies of 0.03 and an inter-observer difference of 0.04. The mean difference in RVEF for seven patients studied on two separate occasions 30 minutes apart was only 0.02. In four patients the mean RVEF measured at rest was 0.44 +/- 0.05 (SEM) and after exercise it was 0.48 +/- 0.06. After infusion of isoprenaline at 1 microgram/min the mean rose to 0.64 +/- 0.04 (p less than 0.02) and after infusion of a new beta 1-sympathomimetic agent, prenalterol, at doses of 1 and 2 mg it was 0.56 +/- 0.02 (p less than 0.02) and 0.59 +/- 0.03 (p less than 0.01) respectively, where the significance levels are relative to the resting values. In nine patients with good ventricular function the vasodilator nifedipine caused right and left ventricular ejection fractions to increase by the same amount; while in six patients with severe impairment of left ventricular function due to ischaemic heart disease the RVEF increased from 0.58 +/- 0.03 to 0.73 +/- 0.03 (p less than 0.01) after 2 mg of prenalterol, but the left ventricular ejection fraction increased only from 0.22 +/- 0.04 to 0.26 +/- 0.04. We conclude that repeated estimation of right ventricular performance is possible by equilibrium radionuclide ventriculography.
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PMID:Can right ventricular performance be assessed by equilibrium radionuclide ventriculography? 613 86

We examined, in conscious dogs, the effects of beta-adrenergic stimulation on measurements of left circumflex coronary arterial diameter and blood flow and on calculations of late diastolic coronary resistance (LDCR) and left circumflex coronary internal cross-sectional area (CSA). Isoproterenol (0.1 microgram/kg) initially decreased mean arterial pressure by 25 +/- 2% (mean +/- SEM), and LDCR by 62 +/- 4%, and increased heart rate by 82 +/- 10%, left ventricular (LV) dP/dt by 79 +/- 12%, and mean coronary blood flow by 85 +/- 5%, while CSA rose slightly. The peak effects on CSA (24 +/- 2%) occurred later, along with decreases in mean arterial pressure (7.4 +/- 1.0%) and LDCR (25 +/-5.3%) and increases in coronary blood flow (14 +/- 2%), LV dP/dt (12 +/- 3%), and heart rate (24 +/- 4%). Pirbuterol (1.0 microgram/kg) induced changes that were qualitatively similar to those induced by isoproterenol. Prenalterol (20 micrograms/kg), a cardioselective beta 1-adrenergic receptor agonist, did not affect mean arterial pressure, but increased heart rate by 40 +/- 5%, LV dP/dt by 72 +/- 10%, mean coronary blood flow by 34 +/- 11%, and CSA by 26 +/- 3%, and decreased LDCR by 29 +/- 5+. Isoproterenol and pirbuterol, but not prenalterol, increased coronary sinus O2 content and decreased A-VO2 difference. After beta 1-adrenergic receptor blockade with atenolol (1 mg/kg), prenalterol no longer induced significant effects, whereas isoproterenol and pirbuterol decreased mean arterial pressure similarly to what was observed prior to blockade, but did not increase LV dP/dt, and induced attenuated increases in mean coronary blood flow, CSA, and decreases in LDCR. Thus, in the intact, conscious animal, large coronary arteries are regulated by beta-adrenergic mechanisms. Surprisingly, a major fraction of large coronary arterial dilation appeared to be either directly or indirectly due to beta 1-adrenergic receptor mechanisms, although beta 2-adrenergic effects were also significant.
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PMID:Regulation of large coronary arteries by beta-adrenergic mechanisms in the conscious dog. 628 97

We compared the effects of single doses of 50 mg atenolol (cardioselective), 40 mg propranolol (nonselective), and placebo on both exercise- and isoproterenol-induced tachycardia in two experiments involving nine normal subjects. Maximal exercise heart rate was reduced from 187 +/- 4(SEM) after placebo to 146 +/- 7 bpm after atenolol and 138 +/- 6 bpm after propranolol, but there were no differences between the drugs. The effects on isoproterenol tachycardia were determined before and after atropine (0.04 mg/kg IV). Isoproterenol sensitivity was determined as the intravenous dose that increased heart rate by 25 bpm (CD25) and this was increased from 1.8 +/- 0.3 micrograms after placebo to 38.9 +/- 8.3 micrograms after propranolol and 8.3 +/- 1.7 micrograms after atenolol. The difference in the effects of the two was significant. After atropine the CD25 was unchanged after placebo (2.3 +/- 0.3 micrograms) and atenolol (7.7 +/- 1.3 micrograms); it was reduced after propranolol (24.8 +/- 5.0 micrograms), but remained different from atenolol. This change with propranolol sensitivity was calculated as the apparent Ka, this was unchanged by atropine (11.7 +/- 2.1 and 10.1 +/- 2.5 ml/ng). These data are consistent with the hypothesis that exercise-induced tachycardia results largely from beta 1-receptor activation that is blocked by both cardioselective and nonselective drugs, whereas isoproterenol activates both beta 1- and beta 2-receptors so that after cardioselective blockade there remains a beta 2-component that can be blocked with a nonselective drug. While there appear to be beta 2-receptors in the human heart, their physiologic or pathologic roles remain to be defined.
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PMID:Evidence for cardiac beta 2-adrenoceptors in man. 629 41

The hemodynamic, hormonal and electrolyte effects of prenalterol, a synthetic selective beta 1 agonist, were studied in six patients with New York Heart Association functional class II and III heart failure. Prenalterol was infused incrementally at 60, 120 and 240 nmol/min, each rate for 24 hours, producing steady-state plasma prenalterol levels of 52 +/- 3, 121 +/- 6 and 194 +/- 9 nmol/1, respectively (mean +/- SEM). Hemodynamic and hormonal measurements were performed before, during and after prenalterol administration under conditions of constant body posture and a regulated intake of dietary sodium and potassium. Prenalterol induced a statistically significant increase in cardiac index (from 2.6 +/- 0.2 to 3.1 +/- 0.3 1/min/m2), with parallel increases in stroke index (from 28 +/- 2 to 34 +/- 2 ml/beat/m2). Forearm blood flow measurements increased (from 2.9 +/- 0.5 to 4.1 +/- 0.6 ml/min/100 g), while calculated systemic vascular resistance fell, as did pulmonary capillary wedge pressure (from 13.7 +/- 1.6 to 10.5 +/- 1.7 mm Hg). The drug did not alter heart rate, arterial pressure, right heart pressures or the frequency of ventricular premature beats. Prenalterol increased plasma renin activity (from 2.9 +/- 0.8 to 6.6 +/- 1.8 nmol/1/hour), angiotensin II (from 59 +/- 12 to 89 +/- 22 pmol/1), urinary aldosterone excretion (from 41 +/- 10 to 78 +/- 34 nmol/day) and plasma insulin (from 10.6 +/- 2.2 to 19.8 +/- 3.9 mU/1). Circulating catecholamines, cortisol, glucose, glucagon or pancreatic polypeptide did not change. Dose-response studies in five patients showed dose-dependent increments in hemodynamic variables, while hormonal changes plateaued at the second dose level. We conclude that prenalterol infusion augments myocardial contractility, reduces systemic vascular resistance, and stimulates insulin release and the renin-angiotensin-aldosterone system.
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PMID:Hemodynamic, hormonal and electrolyte responses to prenalterol infusion in heart failure. 682 3


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