Asymmetry in the control of cardiac performance by dorsomedial hypothalamus.

Dorsomedial hypothalamus (DMH) plays a key role in integrating cardiovascular responses to stress. We have recently reported greater heart rate responses following disinhibition of the right side of the DMH (R-DMH) in anesthetized rats and greater suppression of stress-induced tachycardia following inhibition of the R-DMH in conscious rats [both compared with similar intervention in the left DMH (L-DMH)], suggesting existence of right/left side asymmetry in controlling cardiac chronotropic responses by the DMH. The aim of the present study was to determine whether similar asymmetry is present for controlling cardiac contractility. In anesthetized rats, microinjections of the GABAA antagonist bicuculline methiodide (BMI; 40 pmol/100 nl) into the DMH-evoked increases in heart rate (HR), left ventricular pressure (LVP), myocardial contractility (LVdP/dt), arterial pressure, and respiratory rate. DMH disinhibition also precipitated multiple ventricular and supraventricular ectopic beats. DMH-induced increases in HR, LVP, LVdP/dt, and in the number of ectopic beats dependent on the side of stimulation, with R-DMH provoking larger responses. In contrast, pressor and respiratory responses did not depend on the side of stimulation. Newly described DMH-induced inotropic responses were rate-, preload- and (largely) afterload-independent; they were mediated by sympathetic cardiac pathway, as revealed by their sensitivity to ß-adrenergic blockade. We conclude that recruitment of DMH neurons causes sympathetically mediated positive chronotropic and inotropic effects, and that there is an asymmetry, at the level of the DMH, in the potency to elicit these effects, with R-DMH > L-DMH.

Epileptic seizure-induced hypertension and its prevention by calcium channel blockers: a real-time study in conscious telemetered rats.

Epileptic seizures are accompanied by changes in autonomic function that in turn influence the cardiovascular system (hypertension and bradyarrhythmia). We have studied possible cardioprotective activity (during the ictal state in conscious animals) of valproic acid, nifedipine, and verapamil, alone and in combination, during pentylenetetrazole (PTZ)-induced seizures. Telemetry system was used for recording EEG, blood pressure, and heart rate in conscious, freely moving rats during seizures. We observed that PTZ-induced seizures were accompanied by hypertension and bradyarrhythmia. Pretreatment with valproic acid did not block seizure-induced hypertension and bradyarrhythmia. Nifedipine alone and in combination with valproic acid blocked seizure-induced hypertension and bradyarrhythmia significantly. We also observed that pretreatment with verapamil alone and in combination with valproic acid did not block seizure-induced hypertension and bradyarrhythmia significantly. Our results suggest that pretreatment with nifedipine alone or in combination with valproic acid provides protection against seizure-induced hypertension and bradyarrhythmia.

Simultaneous recording of electroencephalogram and blood pressure in conscious telemetered rats during ictal state.

INTRODUCTION: Seizures are accompanied by autonomic dysfunction which in turn influences cardiovascular variables. A method for simultaneous acquisition of electroencephalogram (EEG) and arterial blood pressure (BP) during seizures in conscious animals has not previously been described. METHODS: The effect of pentylenetetrazole (PTZ) was first studied on isolated rat atria. EEG and BP were then monitored simultaneously in conscious rats, with a chronically implanted radiotelemetric device. Changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) during epileptiform seizures induced by intraperitoneal administration of PTZ were monitored to validate the method. RESULTS: PTZ did not have significant inotropic or chronotropic effect in isolated atria. The radiotelemetry system used to acquire data in unrestrained conscious rats enabled us to study neurological excitation (EEG) and cardiovascular variables (BP and HR) during seizures. Our results demonstrated that this method can be used to study the effect of neuronal excitation on cardiovascular variables and vice versa.

Activation of 5-HT(1A) receptors attenuates tachycardia induced by restraint stress in rats.

To better understand the central mechanisms that mediate increases in heart rate (HR) during psychological stress, we examined the effects of systemic and intramedullary (raphe region) administration of the serotonin-1A (5-HT(1A)) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) on cardiac changes elicited by restraint in hooded Wistar rats with preimplanted ECG telemetric transmitters. 8-OH-DPAT reduced basal HR from 356 +/- 12 to 284 +/- 12 beats/min, predominantly via a nonadrenergic, noncholinergic mechanism. Restraint stress caused tachycardia (an initial transient increase from 318 +/- 3 to 492 +/- 21 beats/min with a sustained component of 379 +/- 12 beats/min). beta-Adrenoreceptor blockade with atenolol suppressed the sustained component, whereas muscarinic blockade with methylscopolamine (50 microg/kg) abolished the initial transient increase, indicating that sympathetic activation and vagal withdrawal were responsible for the tachycardia. Systemic administration of 8-OH-DPAT (10, 30, and 100 microg/kg) attenuated stress-induced tachycardia in a dose-dependent manner, and this effect was suppressed by the 5-HT(1A) antagonist WAY-100635 (100 microg/kg). Given alone, the antagonist had no effect. Systemically injected 8-OH-DPAT (100 microg/kg) attenuated the sympathetically mediated sustained component (from +85 +/- 19 to +32 +/- 9 beats/min) and the vagally mediated transient (from +62 +/- 5 to +25 +/- 3 beats/min). Activation of 5-HT(1A) receptors in the medullary raphe by microinjection of 8-OH-DPAT mimicked the antitachycardic effect of the systemically administered drug but did not affect basal HR. We conclude that tachycardia induced by restraint stress is due to a sustained increase in cardiac sympathetic activity associated with a transient vagal withdrawal. Activation of central 5-HT(1A) receptors attenuates this tachycardia by suppressing autonomic effects. At least some of the relevant receptors are located in the medullary raphe-parapyramidal area.