A Method of Stimulating the Complete Sympathetic Outflow From the Spinal Cord to Blood Vessels in the Pithed Rat

Abstract

The effects of sympathetic nerve stimulation on blood vessels have been studied in a variety of ways. The vascular beds of various organs or regions have been perfused either in vivo or in vitro with blood or saline and the pressor response to stimulation of the operatively exposed sympathetic nerves measured. In other experiments the response of isolated arteries to stimulation of their sympathetic nerves has been studied. None of these methods gives information on the integrated response of the blood vessels constituting the peripheral resistance to stimulation of the entire sympathetic outflow. Furthermore, in experiments stimulating exposed sympathetic nerves, the operative interference in making the preparation may itself affect the vascular responses.The technique here described involves no further operative interference beyond that involved in pithing the animal and recording blood pressure, and the pressor responses obtained probably involve the entire vasculature and its sympathetic nerve supply. In principle, the steel pithing rod is used as one electrode to stimulate spinal nerve roots.Large rises in arterial blood pressure can be produced and the method is particularly suited to studying the action of drugs. METHODSRats (150-350 g) were anaesthetized with ether following atropine (1 mg/kg intraperitoneally). The trachea was cannulated, and animals pithed through one orbit with a steel rod and immediately artificially respired. Blood pressure was recorded from a carotid artery using a Condon mercury manometer and one femoral vein was cannulated for the administration of drugs. Those parts of the pithing rod which lay in the sacral and cervical regions of the spinal cord were coated with high-resistance varnish to restrict stimulation to the thoraco-lumbar region. The appropriate parts of the rod to be coated were determined by exposing the pithing rod as it lay in the vertebral canal of a rat of similar size. In all animals excitation included the upper lumbar region as shown by twitching of the lower limbs. Any residual effects of stimulating sacral or vagal parasympathetic fibres by spread of the stimulating current were eliminated by a second injection of atropine (1 mg/kg intravenously). In preliminary experiments, premedication with atropine was omitted and the effect of this drug on the vasopressor response to nerve stimulation studied. Atropine did not reduce the pressor response (Fig. 1A). Electrical stimulation affects the motor fibres in the ventral roots, causing twitching of skeletal muscle. In addition to interfering with respiration, these twitches on * Henry Head Fellow.

Cardiovascular reactivity in the experimental hypertensive rat

“…Pressor agents were injected every 20 min and the mean of two responses calculated. In some experiments, pithed preparations were used for stimulation of the entire sympathetic outflow (Gillespie & Muir, 1967); submaximal stimulation from a Multitone stimulator at strengths of 15-30 V, 0 03 ms duration and frequencies of 3 Hz and 6 Hz were applied for periods of 18 seconds. Stimulation was repeated at not less than 10 min intervals.…”

Inhibitory Effects of Clonidine on Responses to Sympathetic Nerve Stimulation in the Pithed Rat

“…The pithing rod was used to stimulate either the entire sympathetic outflow (Gillespie & Muir, 1967) or discrete segments of the spinal cord (Gillespie, Maclaren & Pollock, 1970). The tissues to which the sympathetic outflow was stimulated and the stimulus parameters used are shown in Table 1.…”

Proceedings of the British Pharmacological Society

“…This hypotensive effect of a-methyldopa was not prevented by the destruction of peripheral adrenergic nerve endings with 6-hydroxydopamine. Furthermore, in genetic hypertensive rats the responses to stimulation of the entire sympathetic outflow (Gillespie & Muir, 1967) were not influenced by pretreatment with a-methyldopa (300 mg/kg i.p. ).…”