Various opioids were used to investigate the role they might play in the cardiovascular responses to fatiguing isometric contractions. Changes in blood pressure were measured in cats anaesthetised with α-chloralose. Fatiguing isometric contractions of the hind limb muscles (ergoreceptor activation) were generated using a microprocessor controlled stimulator (50 Hz, 0.2 ms, 200-800 mV). Baroreceptor inactivation was elicited by carotid artery occlusion. Muscle contraction caused an increase in mean arterial pressure of 51 (SEM 12) mm Hg and carotid occlusion an increase of 56(9) mm Hg above resting levels in control conditions. Injection of dynorphin (0.5-5.0 μg·5 μl-1) into the cerebral aqueduct just rostra1 to the 4th ventricle eliminated the pressor response to muscular contraction (mean arterial pressure at rest, 80-118 mm Hg: on fatigue, 72-129 mm Hg) but did not affect the pressor response to carotid occlusion in the same cats. Similarly, injections of met-enkephalin (1-100 μg·5 μl-1) or β-endorphin (10-100 μg·5 μl-1) eliminated the ergoreceptor induced changes in mean arterial pressure during isometric contractions but had no effect on the changes caused by carotid occlusion. Pressor responses to nerve crush were not eliminated. These results support the suggestion that a catecholaminergic-opioidergic pathway in part mediates the cardiovascular responses to ergoreceptor afferent but probably not baroreceptor afferent input.

Summary: The effects of an alpha2 adrenoceptor blocker, yohimbine, and an alpha1 adrenoceptor blocker, phenoxybenzamine, and the central alpha2 adrenoceptor agonist, clonidine, on changes in arterial blood pressure and heart rate were studied during fatiguing muscular contractions to determine whether an adrenergic-opioidergic system might be involved in the mediation of cardiovascular function. Fatiguing contractions of the gastrocnemius and plantaris muscles of cats caused an increase in mean arterial blood pressure to 150-170 mmHg from resting values of 110-120 mmHg. Injection of clonidine into the cerebral aqueduct eliminated the increase in blood pressure; this effect was dose dependent. Naloxone antagonised the effects of the highest dose of clonidine (5 μg). Injections of yohimbine (1 μg) into the cerebral aqueduct had no significant effect on this pressor response. Yohimbine (1 μg) effectively counteracted the antipressor effects of clonidine when the two drugs were injected together until higher doses of clonidine (2-5 μg) were used. Phenoxybenzamine had no effect on the pressor response itself but unlike yohimbine was able to attenuate the effects of clonidine only when injected together. These data suggest that activation of muscle ergoreceptor afferent nerve fibres (group III and IV fibres) during muscular contractions may cause an increase in arterial blood pressure by interfering with an inhibitory adrenergic-endorphinergic pathway in the medullary region of the brainstem.