Acidaemia produced by spinal stimulation in the pithed rat

Area of Science:

• Neuroscience
• Physiology
• Pharmacology

Background:

• The pithed rat preparation is used to study adrenergic mechanisms.
• Electrical stimulation of spinal nerves can induce physiological responses.

Purpose of the Study:

• To investigate the mechanisms underlying the fall in arterial blood pH (acidaemia) induced by spinal nerve stimulation in pithed rats.
• To determine the roles of skeletal muscle, adrenal medulla, and sympathetic nerve endings in this response.
• To identify the adrenoceptor subtypes involved.

Main Methods:

• Electrical stimulation of the thoraco-lumbar spinal nervous outflow in pithed rats.
• Pharmacological interventions including gallamine (muscle relaxant), adrenalectomy, guanethidine (sympathetic neurotoxin), phenoxybenzamine (alpha-blocker), and propranolol (beta-blocker).
• Measurement of arterial blood pH to assess the acidaemic response.

Main Results:

• Electrical stimulation resulted in a significant fall in arterial blood pH.
• The acidaemic response was partially mediated by skeletal muscle contraction, as blocked by gallamine.
• Adrenalectomy and guanethidine reduced the residual acidaemic response, indicating roles for adrenal catecholamines and sympathetic noradrenaline.
• Combined alpha- and beta-adrenoceptor blockade almost abolished the acidaemia, suggesting involvement of both receptor types.

Conclusions:

• The acidaemic response to spinal nerve stimulation in pithed rats is multifactorial, involving skeletal muscle, adrenal catecholamines, and sympathetic noradrenaline.
• Catecholamines mediate this response via both alpha- and beta-adrenoceptors.
• These findings have implications for the use of the pithed rat model in assessing drugs that affect adrenergic mechanisms.