ABSTRACT
Altered sympathetic nervous system activity has been implicated often in hypertension. We examined short-term potentiation [posttetanic potentiation (PTP)] and long-term potentiation (LTP) in the isolated superior cervical ganglia (SCG) from Sprague-Dawley (SD) rats given vehicle, digoxin, or ouabain by subcutaneous implants as well as in animals with ouabain-induced hypertension (OHR), and inbred Baltimore ouabain-resistant (BOR) and Baltimore ouabain-sensitive (BOS) strains of rats. Postganglionic compound action potentials (CAP) were used to determine PTP and LTP following a tetanic stimulus (20 Hz, 20 s). Baseline CAP magnitude was greater in ganglia from OHR than in vehicle-treated SD rats before tetanus, but the decay time constant of PTP was significantly decreased in OHR and in rats infused with digoxin that were normotensive. In hypertensive BOS and OHR, the time constants for the decay of both PTP and LTP (t(L)) were increased and correlated with blood pressure (slope = 0.15 min/mmHg, r = 0.52, P < 0.047 and 6.7 min/mmHg, r = 0.906, P < 0.0001, respectively). In BOS and OHR, t(L) (minutes) was 492 +/- 40 (n = 7) and 539 +/- 41 (n = 5), respectively, and differed (P < 0.05) from BOR (257 +/- 48, n = 4), SD vehicle rats (240 +/- 18, n = 4), and captopril-treated OHR (370 +/- 52, n = 5). After the tetanus, the CAP at 90 min in BOS and OHR SCG declined less rapidly vs. SD vehicle rats or BOR. Captopril normalized blood pressure and t(L) in OHR. We conclude that the duration of ganglionic LTP and blood pressure are tightly linked in ouabain-dependent hypertension. Our results favor the possibility that enhanced duration of LTP in sympathetic neurons contributes to the increase in sympathetic nerve activity in ouabain-dependent hypertension and suggest that a captopril-sensitive step mediates the link of ouabain with LTP.
Subject(s)
Blood Pressure/physiology , Hypertension/physiopathology , Neuronal Plasticity/physiology , Ouabain/pharmacology , Superior Cervical Ganglion/physiology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Blood Pressure/drug effects , Digoxin/pharmacology , Disease Models, Animal , Electrophysiology , Humans , Hypertension/chemically induced , In Vitro Techniques , Long-Term Potentiation , Male , Rats , Rats, Inbred Strains , Rats, Sprague-Dawley , Superior Cervical Ganglion/drug effectsABSTRACT
Substances of abuse exert adrenergic and/or depressant actions on the cellular processes responsible for cytosolic calcium overload. This investigation attempted to determine whether substances of abuse, through catechol-mediated effects or cellular actions, elicit or inhibit the production of arrhythmias caused by delayed afterdepolarizations (DADs) and triggered activity (TA). The papillary muscles of rats and Purkinje fibers of dogs were superfused in vitro with Tyrode's solution at 37 degrees C. Intracellular microelectrodes were used to record membrane potentials. Overdrives failed to induce DADs and TA in the canine Purkinje fibers exposed to either Tyrode's solution alone, or containing ethanol or harmine. Instead, ethanol and harmine inhibited DADs and TA induced by overdrives in the presence of strophanthidin. On the contrary, in the presence of acetaldehyde and amphetamine, overdrives did produce TA, which was inhibited by propranolol. In conclusion, substances of abuse may either elicit or inhibit the production of DADs and TA, depending on the balance between adrenergic and depressant actions on the cellular mechanisms responsible for the calcium overload of the cytosol.
Subject(s)
Anti-Arrhythmia Agents/pharmacology , Arrhythmias, Cardiac/chemically induced , Central Nervous System Depressants/pharmacology , Central Nervous System Stimulants/pharmacology , Papillary Muscles/drug effects , Purkinje Fibers/drug effects , Amphetamine , Animals , Anti-Arrhythmia Agents/adverse effects , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/physiopathology , Calcium/metabolism , Central Nervous System Depressants/adverse effects , Central Nervous System Stimulants/adverse effects , Cytosol/drug effects , Cytosol/metabolism , Dogs , In Vitro Techniques , Male , Membrane Potentials/drug effects , Microelectrodes , Papillary Muscles/metabolism , Papillary Muscles/physiopathology , Purkinje Fibers/metabolism , Purkinje Fibers/physiopathology , Rats , Rats, Sprague-DawleyABSTRACT
The main objective of this investigation was to clarify the mechanisms of the acute in vitro actions of amphetamine (AMP) on cardiac electrophysiology. Concentrations of AMP ranging from those considered clinically therapeutic to those considered toxic were tested in isolated rat sinoatrial tissues while recording membrane potentials with intracellular microelectrodes. In preparations beating spontaneously, 6.8 nM-2.71 microM AMP exerted a positive chronotropic action that was blocked by propranolol. The positive chronotropic action of 5.43 microM AMP was smaller than that of 2.7 microM AMP and was reversed by propranolol. Neither phentolamine nor atropine blocked this depressant action of AMP. It is concluded that the positive chronotropic action of AMP was beta-adrenergic and that beta-adrenergic block unmasked a negative chronotropic action of a high concentration of AMP, which was neither alpha-adrenergic nor muscarinic. In atrial fibers driven at a constant rate, 54.3 nM AMP prolonged the action potential duration (APD), without affecting the resting membrane potential (RMP), the action potential amplitude (APA), or the maximum velocity of phase 0, while 5.43 microM AMP reduced RMP, APA, and the maximum velocity of phase 0, and increased APD. The prolongation of APD, as well as the decreases of RMP and APA, was not abolished by propranolol, phentolamine, or 4-aminopyridine. Conversely, nifedipine abolished the effects of AMP on all three parameters. In general, AMP produced mainly a prolongation of the action potential. Only a high concentration of AMP decreased RMP and depressed phase 0 of the action potential. The effect of AMP on APD, RMP, and APA essentially involved increasing the influx of calcium through the L-type channels in the sarcolemma.
