Subject(s)
Internal Medicine/trends , Awards and Prizes , Congresses as Topic , Faculty, Medical , History, 20th Century , History, 21st Century , Humans , Hungary , Internal Medicine/history , Natriuretic Agents/history , Natriuretic Agents/metabolism , Physician-Patient Relations , Societies, MedicalABSTRACT
This study tested the hypothesis that rat adrenocortical secretion of endogenous ouabain-like factor (OLF) is regulated by nicotinic mechanisms. OLF secreted by dispersed cell suspensions of zona glomerulosa (ZG) and fasciculata/reticularis (ZFR) cells was found to co-elute with authentic ouabain by reverse phase HPLC; OLF concentrations in cell supernatants were measured by radioimmunoassay. Nicotine (10(-6) - 10(-3) M) stimulated significant OLF secretion in rat adrenocortical cells. Acetylcholine (10(-7) - 10(-4) M) and eserine (10(-7) - 10(-3) M) stimulated OLF secretion in ZG cells at lower concentrations and stimulated at higher concentrations. Acetylcholine had no effect on ZFR secretion of OLF, but eserine stimulated OLF secretion. ACTH (10(-8) M) strongly potentiated the OLF stimulatory effect of nicotine in ZG cells; however significant interactions between nicotine and ACTH or angiotensin II on OLF secretion in ZFR cells were not apparent. The ganglionic blockers hexamethonium and mecamylamine further potentiated the effect of nicotine, implicating nicotinic acetylcholine receptors (nAChRs) in regulation of OLF secretion. The alpha7-receptor antagonist methyllycaconitine (MLA) dose-dependently inhibited the effect of nicotine in the ZG cells, and in ZFR cells MLA potentiated nicotine-induced OLF secretion. These data suggest that nicotinic regulation may underlie OLF secretion by rat adrenocortical cells, and strongly suggest presence of functional nicotinic acetylcholine receptors on these cells.
Subject(s)
Aconitine/analogs & derivatives , Adrenal Cortex/metabolism , Receptors, Nicotinic/metabolism , Saponins/metabolism , Acetylcholine/pharmacology , Aconitine/pharmacology , Adrenal Cortex/drug effects , Animals , Cardenolides , Digoxin , Dose-Response Relationship, Drug , Drug Synergism , Hexamethonium/pharmacology , Male , Mecamylamine/pharmacology , Nicotine/pharmacology , Nicotinic Antagonists/pharmacology , Physostigmine/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Nicotinic/drug effectsABSTRACT
Endothelin-1 (ET-1) is known to have a direct arrhythmogenic effect in the mammalian heart. Diabetes mellitus is accompanied by a series of endothelial and cardiac disfunctions; however, little is known about ET-1-induced direct arrhythmias in diabetes mellitus. Therefore, we infused ET-1 (33 pmol/min) into the left anterior descending coronary artery of 28 mongrel dogs, and measured basic hemodynamic parameters, coronary flow and an electrocardiogram. Diabetes mellitus was induced by alloxan (Group 4) and experiments were carried out 8 weeks later. Metabolically healthy dogs served as controls (Group 2). In a further control group, local hyperglycemia was induced by intracoronary glucose infusion (Group 3). ET-1 infusion induced prolongation of the QT-time and frequency-adjusted QT-time in all groups. Other electrophysiological parameters were comparable between the groups. This was followed by the occurence of ventricular premature beats, coupled extra-beats and later sustained ventricular tachycardia. Most of the experiments were terminated by ventricular fibrillation. The onset of arrhythmias was shorter in diabetic dogs as compared with control and locally hyperglycemic animals (18 +/- 8 minutes versus 24 +/- 8 minutes and 30 +/- 28 minutes, P < 0.05). However, there was no difference in the number of ventricular fibrillations, and the total elapsed time until the termination of the experiments. Therefore, the diabetic heart seems to be more prone to ET-1-induced arrhythmias and this is probably not a result of locally high glucose concentrations.
Subject(s)
Diabetes Mellitus, Experimental/complications , Hemodynamics , Tachycardia, Ventricular/etiology , Ventricular Fibrillation/etiology , Ventricular Premature Complexes/etiology , Animals , Blood Pressure , Coronary Circulation , Diabetes Mellitus, Experimental/physiopathology , Dogs , Electrocardiography , Endothelin-1/administration & dosage , Glucose/administration & dosage , Heart Rate , Infusions, Parenteral , Risk Factors , Tachycardia, Ventricular/chemically induced , Tachycardia, Ventricular/physiopathology , Time Factors , Ventricular Fibrillation/chemically induced , Ventricular Fibrillation/physiopathology , Ventricular Premature Complexes/chemically induced , Ventricular Premature Complexes/physiopathologyABSTRACT
Compared to healthy adults, elevated levels of endogenous ouabain-like factor (OLF) have already been shown in the cord blood, and a role of OLF in the maintenance of high Na(+) excretion by reducing tubular sodium reabsorption during intrauterine life was suggested. In this study, we aimed to measure OLF cord blood levels of premature and mature newborns to provide further data on the possible physiological significance of this compound in neonates. OLF was assessed in the cord blood of newborns (28-41 weeks) and in the blood of healthy adults using ouabain radioimmunoassay. HPLC was employed to isolate endogenous OLF. Newborns had about twelve times higher OLF levels than healthy adults (41.96 +/- 4.64 vs. 3.1 +/- 1.1 pg/ml, p < 0.001). Further, there was a highly significant correlation (p < 0.004) between maturity and OLF concentration; OLF level increased with gestational age, however there was a rapid drop in its concentration at week 39 (43.26 +/- 7 vs. 35.47 +/- 1.84 pg/ml, p = NS). Further studies are needed to evaluate the physiological relevance of higher OLF in preterm versus mature newborns.
