Summary: The possible involvement of an adrenergic-endorphin system in the mediation of the pressor response to isometric muscular contraction was studied in cats. Fatiguing contractions of the gastrocnemius and plantaris muscles caused an increase in the mean arterial blood pressure by 35 to 70 mmHg. Intravenous infusion (30 μg·kg-1) as well as intracisternal injection (2.5 μg) of clonidine-HCl eliminated the pressor response to muscular contraction. In both sets of experiments, the mean blood pressure remained at the resting level throughout the duration of the isometric contraction. Injection of naloxone (0.5 μmol·litre-1) into the cisterna magna did not alter the resting blood pressure and did not affect the rise in mean arterial pressure during muscle contractions. Intracisternal injection of naloxone (0.5 μmol·litre-1) prior to an intracisternal injection of clonidine (2.5 μg) did not alter the resting blood pressure but effectively antagonised the anti-pressor effects of clonidine during fatiguing isometric contractions. These data may indicate that activation of muscle "ergoreceptor" afferents (group III and IV fibres) during muscular contraction may cause an increase in the arterial blood pressure by interfering with an inhibitory adrenergic-endorphinergic pathway in the brainstem.

Experiments were performed to determine to what extent increments in esophageal and abdominal pressure would have on arterial blood pressure during fatiguing isometric exercise. Arterial blood pressure was measured during handgrip and leg isometric exercise performed with both a free and occluded circulation to active muscles. Handgrip contractions were exerted at 33 and 70% MVC (maximum voluntary contraction) by 4 volunteers in a sitting position and calf muscle contractions at 50 and 70% MVC with the subjects in a kneeling position. Esophageal pressure measured at the peak of inspirations did not change during either handgrip or leg contractions but peak expiratory pressures increased progressively during both handgrip and leg contractions as fatigue occurred. These increments were independent of the tensions of the isometric contractions exerted. Intra-abdominal pressures measured at the peak of either inspiration or expiration did not change during inspiration with handgrip contractions but increased during expiration. During leg exercise, intraabdominal pressures increased during both inspiration and expiration, reaching peak levels at fatigue. The arterial blood pressure also reached peak levels at fatigue, independent of circulatory occlusion and tension exerted, averaging 18.5-20 kPa (140-150 mm Hg) for both handgrip and leg contrations. While blood pressure returned to resting levels following exercise with a free circulation, it declined by only 2.7-3.8 kPa after leg and handgrip exercise, respectively, during circulatory occlusion. These results indicate that straining maneuvers contribute 3.5 to 7.8 kPa to the change in blood pressure depending on body position.

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.

This study compared whether activation of muscle ergoreceptor afferents caused by isometric muscle contraction, activation of baroreceptor afferents induced by i.v. infusion of phenylephrine, or baroreceptor afferent inactivation, caused by carotid artery occlusion, elicit similar patterns of c-Fos induction in brainstem areas. Adult cats were anesthetized with α-chloralose, and in each case, the experimental intervention caused an increase in the arterial blood pressure. There were two sets of control experiments: in both, animals underwent the same surgical procedures but then either remained at rest for the entire study, or the tibial nerve was stimulated, as in the contraction group, following muscle paralysis with tubocurarine. Following the procedures, animals rested for 90 min to allow neuronal expression of c-Fos. Control cats showed very little c-Fos immunoreactivity (c-Fos-ir) in the brainstem. Muscle contraction induced c-Fos-ir expression mainly in the nucleus tractus solitarius, lateral reticular nucleus, lateral tegmental field, vestibular nucleus, subretrofacial nucleus, spinal trigeminal tract and in a lateral region of the periaqueductal grey (P 0.5-1.0). The majority of the c-Fos-ir was found in brainstem areas contralateral to the contracted muscle. In addition, muscle contraction induced c-Fos-ir in the dorsal horns of spinal segments L6-S1 on the ipsilateral side of the spinal cord. Phenylephrine infusion caused c-Fos-ir expression in the nucleus tractus solitarius, spinal trigeminal tract, solitary tract, and dorsal motor nucleus of the vagus. No c-Fos-ir was apparent in the periaqueductal grey. Carotid occlusions induced c-Fos-ir expression in the area postrema, nucleus tractus solitarius, solitary tract, and spinal trigeminal tract. Expression was bilateral. Areas that exhibited c-Fos-ir correspond to sites previously reported to release various neuropeptides in response to muscle contraction or carotid occlusions. These results indicate that the exercise pressor reflex and baroreflex activate similar, but not completely identical, sites in the brainstem.

Study objective - The aim was to determine whether areas in the periaqueductal grey matter, medial dorsal raphé, or ventrolateral medulla might be involved with the integration of blood pressure and heart rate during isometric exercise.Design - Cats were anaesthetised with α chloralose (75 mg·kg-1) and catheters inserted into the right jugular vein and carotid artery. Isometric contractions were generated using a microprocessor controlled stimulator and sleeve electrode around the tibial nerve. Bilateral lesions were made in the dorsal periaqueductal grey matter (P1.0, LR 2.0, HD + 1.5 mm) or two sites in the ventrolateral medulla (P12.0, RL 2.0, HD -10 mm; or P12.0, RL 2.0, HD -8.5 mm). Lesions were also made in the medial dorsal raphé nuclei (P1.0, RL 0.0, HD +1.5 mm). Clonidine was injected into the cerebral aqueduct to determine whether it would exert an antipressor effect during muscle contraction after the lesions were made. Only one site of lesion was made in a group of animals. Bilateral injections of clonidine (250 ng in 0.5 μl) were made into the intact ventrolateral medulla (P11.5, RL 4.0, HD -8.5 mm) to explore its role further. Fatiguing contractions were performed before and after the lesions were made, or clonidine was injected, and changes in arterial blood pressure and heart rate were measured. Verification of the lesion sites or the microinjection sites, and the extent of the lesion or spread of the clonidine, was made from histological examination of brain tissue after each experiment.Experimental material - Adult cats of either sex, n = 20, weight 2.4 (SD 0.4) kg, were used.Measurements and main results - Fatiguing isometric contractions in control conditions caused mean arterial pressure to increase by 45-50 mm Hg and heart rates by 20-25 beats·min-1. Bilateral lesions in the dorsal periaqueductal grey matter did not alter resting mean arterial pressure but attenuated the pressor response during contractions. Injections of clonidine into the cerebral aqueduct had no further antipressor effects after the lesions. Lesions of the medial dorsal raphé nuclei or injections of clonidine into the intact medial dorsal raphé nuclei did not affect the pressor response to fatiguing isometric contractions. Injections of clonidine into the intact ventrolateral medulla eliminated the pressor response to isometric contractions. Bilateral lesions of the ventrolateral medulla near the rostral lateral border of the inferior olivary tract nuclei (P12.0, LR 2.0, HD -10 mm) also attenuated the muscle pressor response, while subsequent injections of clonidine into the cerebral aqueduct depressed the changes in blood pressure further.Conclusions - Ergoreceptor information may be processed through the periaqueductal grey matter through the ventrolateral medulla to control arterial blood pressure during isometric exercise to fatigue.