To assess the possibility of stimulating Ca2+-activated K+ channels, marine fish erythrocytes were incubated at 20-22 degrees C in saline containing a Ca2+-ATPase inhibitor (orthovanadate), a Ca2+ ionophore (A23187), propranolol or Pb2+. Incubation of the cells for up to 2 h under control conditions or in the presence of 5 mM NH4VO3 and 1 mM Ca2+ did not affect the intracellular K+ and Na+ concentrations. About 50% cellular K+ was lost from erythrocytes incubated in the presence of 0.01 mM A23187, 1 mM EGTA and 0.4-1.0 mM Ca2+. There was a significant loss of cellular K+ after the addition of 0.05-0.2 mM propranolol to the incubation medium. The stimulatory effect of propranolol on the K+ efflux was independent of external Ca2+. Blockers of Ca2+ transport, verapamil and Co2+, caused only a small decrease in the K+ loss induced by propranolol. The treatment of erythrocytes with 1-2 microM Pb2+ led to a minor K+ loss, but at a Pb2+ concentration of 20-50 microM, about 70% cellular K+ was lost. The K+ efflux induced by propranolol or Pb2+ was completely blocked by 1 mM quinine. The induced K+ loss from the erythrocytes was accompanied by a slight increase in the intracellular Na+ concentration. These data indicate the possibility of inducing Ca2+- and Pb2+-activated potassium channels in erythrocytes of S. porcus. A distinctive feature of the cells is a high sensitivity to propranolol, which activates K+ channels in the absence of external Ca2+.
Siberian lemmings seem to have lesser noradrenaline (NA) calorigenic action and higher beta-adrenergic "asymmetry" of catecholamine calorigenic effects than the cold- and warmth-adapted laboratory rodents. Selective inhibition of catecholamine effects by beta-adrenoblocking drug propranolol, obvious potentiation of NA effect by caffeine, and compensatory increasing of thermoregulatory musclar contractile activity during the blockade of betaadrenoreceptors under cooling suggest the domineering of betaadrenergic mechanisms of thermogenesis in siberian lemmings and their high thermoregulatory lability.
We have examined direct effects of catecholamines on testicular testosterone production in a seasonally breeding species, the Siberian hamster, Phodopus sungorus. Testicular parenchyma from gonadally active long photoperiod (LD)-exposed and gonadally regressed short photoperiod (SD)-exposed animals was incubated for 6 h with norepinephrine, epinephrine, beta-adrenoceptor agonist isoproterenol, or alpha-adrenoreceptor agonist phenylephrine (all at 10 microM), as well as with various concentrations of norepinephrine (10 nM-10 microM), and 10 microM norepinephrine with or without hCG (0.7, 3.1, and 12.5 mIU/ml). In addition, effects of alpha-adrenoreceptor antagonist prazosin and beta-adrenoreceptor antagonist propranolol (50 microM) were tested in the incubations containing 10 microM norepinephrine. In the incubations of testes from both LD and SD Siberian hamsters, norepinephrine was most effective in stimulating testosterone production, followed by epinephrine and phenylephrine, while isoproterenol failed to increase testosterone accumulation. The stimulatory effects of norepinephrine were dose-dependent and were prevented by coincubation with prazosin, but not affected by coincubation with propranolol. In combination with various doses of hCG, norepinephrine failed to stimulate testosterone production above the levels obtained with hCG alone. These data indicate that the testicular receptors mediating the action of catecholamines on testicular steroidogenesis in Phodopus sungorus are of the alpha 1-subtype, a result in accordance with a previous study in the golden hamster. However, the results of the present study are strikingly different from the findings obtained in the golden hamster in terms of the effects of photoperiod on the responsiveness of testicular steroidogenesis to catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial ischemia, electrolyte changes, and fluctuations in autonomic tone may play an important role in the presentation of malignant ventricular arrhythmias. beta-Adrenoceptor blocking agents have been shown to decrease the incidence of ventricular fibrillation and sudden cardiac death in patients with coronary artery disease. Therefore we investigated the changes in myocardial metabolism and transcardiac electrolytes during simulated ventricular tachycardia before and after beta-adrenergic blockade. Six patients with normal coronary arteries (group 1) and 12 patients with documented coronary artery disease (group 2) were included in the study. The right ventricle was paced with electrode catheters to a constant cycle length of 400 msec for 3 minutes. Blood samples were withdrawn simultaneously from the coronary sinus and femoral artery to determine the transcardiac differences in metabolic variables and electrolytes before the pacing, at the end of the pacing, and 2 minutes thereafter. After pacing, the patients were given intravenous propranolol (0.15 mg/kg), and the protocol was repeated. Intraarterial blood pressure and electrocardiogram were monitored continuously. There was a rapid decline of the mean arterial blood pressures after initiation of the pacing in both study groups, whereafter the pressures began to rise. Propranolol somewhat blunted the blood pressure recovery, especially in group 2. Norepinephrine levels increased during the pacing in both patient groups, and the increase was accentuated by beta-adrenergic blockade. The femoroarterial coronary sinus difference in lactate turned negative, and pH, PCO2 and potassium differences increased in group 2 during pacing. However, the myocardial energy state remained relatively good as estimated from the nonsignificant change in the transcardiac differences of the plasma adenosine catabolites. There were no changes in the metabolic variables or transcardiac electrolytes in group 1 patients during pacing. Propranolol did not prevent the metabolic ischemia, but it did prevent the pacing-induced decrease in coronary sinus potassium and increase in transcardiac potassium difference. Propranolol also decreased arterial levels of free fatty acids and their extraction in group 2 patients during pacing. In conclusion, blood pressure decay during simulated ventricular tachycardia is followed by instantaneous sympathoadrenergic activation. In patients with coronary artery disease, this process is accompanied by metabolic ischemia and net transfer of extracellular potassium into the intracellular space. The metabolic and electrolyte changes may result in alterations of electrophysiologic millieau, thereby also modifying the clinical characteristics of ventricular tachycardia. Propranolol decreases arterial levels of free fatty acids and prevents changes in transcardiac electrolytes observed in coronary artery disease patients during simulated ventricular tachycardia. These effects of propranolol may be of clinical significance.
[Content of fibroblasts, macrophages, granulocytes and lymphocytes in the connective tissue regenerate of the skin in wound healing as affected by noradrenaline, acetylcholine, propranolol and atropine]
Effects of acetylcholine, noradrenaline, atropine and propranolol on cell number in connective tissue regenerates of the skin in wound healing were studied in white rats. Noradrenaline causes the decrease of inflammatory reaction, fibroblast content in regenerate and basophilia of their cytoplasm. Acetylcholine conversely increases cell reaction, but slows down the re-modelling of connective tissue regenerate. The definite dynamic balance between catecholamine and acetylcholine systems of reparation processes regulation in wound healing is noted. This balance could deviate under external influences. The expression of various cellular element reaction to the dermal regenerate on adreno- and cholinotropic influences tends to change during wound healing.
There are several different experimental systems for screening of in vitro inhibitory potency of drugs under development. In this study we compared three different types of cytochrome P450 (CYP) inhibition tests: the traditional single substrate assays, the fluorescent probe method with recombinant human CYPs, and a novel n-in-one technique. All major hepatic drug-metabolizing CYPs were included (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4). Six compounds (sotalol, propranolol, citalopram, fluoxetine, oxazepam and diazepam) were selected for detailed comparisons. The IC50 values of each of these compounds were measured using the three assay types. The inhibitory potencies of these model drugs were generally within the same order of magnitude and followed similar inhibition profiles in all the assay types. Clinically observed inhibitory interactions, or lack thereof, were predictable with all three assays. Comparison of potencies of 'diagnostic' inhibitors revealed also some notable differences between the assays, especially regarding CYP2E1. The potency of inhibitors towards CYP3A4 was dependent on the substrate and reaction measured. Generally all three assays gave reasonably comparable results, although some unexplained differences were also noted.
Heart rate (HR) is higher during dynamic arm exercise than during leg exercise at equal oxygen consumption levels, but the physiological background for this difference is not completely understood. The vagally mediated beat-to-beat R-R interval fluctuation decreases until the level of approximately 50% of maximal oxygen consumption during an incremental bicycle exercise, but the vagal responses to arm exercise are not well known. Changes in autonomic modulation of HR were compared during arm and leg exercise by measuring beat-to-beat R-R interval variability from a Poincaré plot normalized for the average R-R interval (SD1n), a measure of vagal activity, in 14 healthy male subjects (age 20 +/- 4 years) who performed graded bicycle and arm cranking tests until exhaustion. Seven of the subjects also performed the dynamic arm and leg tests after beta-adrenergic blockade (propranolol 0.2 mg kg-1 i.v.). More rapid reduction occurred in SD1n during the low-intensity level of dynamic arm exercise than during dynamic leg exercise without beta-blockade (e.g. 11 +/- 6 vs. 20 +/- 10 at the oxygen consumption level of 1.2 l min-1; P
The investigation carried out on mature rabbits under conditions of beta-adrenoreceptors' blocking by obsidan has revealed that 12-hour immobilization caused neutrophilic leukocytosis in the peripheral blood, degranulation of neutrophils, increase of acid phosphatase activity. These changes occurred much earlier as compared with those in the control group were more pronounced and lasted for a less period of time. Consequently, beta-receptors are the necessary components in the formation of stress-syndrome under the influence of an +non-infectious stressor.