K. J. Rybicki

Pressor reflex response to static muscular contraction: Its afferent arm and possible neurotransmitters

Static muscular contraction has been shown to increase cardiovascular and ventilatory function in reflex manner. The sensory arm of this reflex arc is comprised of group III and IV muscle afferents. The discharge properties of these muscle afferents whose activation causes the pressor reflex response to contraction were investigated. Group III afferents were more responsive to mechanical stimuli, such as tendon stretch and probing their receptive fields than were group IV afferents. In contrast, group III afferents were less responsive to ischemic contraction than were group IV afferents. Equal percentages of group III and IV afferents were stimulated by potassium, lactic acid and arachidonic acid, each of which are metabolic products of contraction. Adenosine, phosphate and lactate, however, had no effect on the discharge of the afferents. Intrathecal injection of antagonists or antibodies to substance P and somatostatin attenuated the pressor response to contraction by about half, a finding that suggests a role for these 2 peptides in the spinal transmission of the reflex.

Attenuation of the reflex pressor response to muscular contraction by a substance P antagonist.

In chloralose-anesthetized cats, we found that D-Pro2-D-Phe7-D-Trp9-substance P (40-100 micrograms), injected intrathecally, reduced the reflex pressor response to static muscular contraction by more than half.

Stimulation of group III and IV muscle afferents reflexly decreases total pulmonary resistance in dogs

Although previous investigations have shown that stimulating group III and IV afferents reflexly decreased transverse tension from the trachealis muscle, these measurements provided no functional information about airway caliber. We therefore electrically stimulated gracilis muscle afferents in paralyzed, chloralose anesthetized dogs while recording total pulmonary resistance breath by breath. In addition, we recorded compound action potentials to determine which afferents were stimulated by current intensities of 3, 5, 20, 70 and 200 times motor threshold. We found that stimulating (20 Hz) the nerves at 3 times threshold, a current intensity which activated only group I and II afferents, had no effect on total pulmonary resistance, whereas stimulating the nerves at 5, 20 and 70 times threshold, current intensities which activated group I, II and III afferents, significantly decreased this variable. Stimulating the nerves at 200 times threshold, a current intensity which activated group IV as well as group I, II and III afferents, decreased total pulmonary resistance significantly more than did stimulating the nerves at 5, 20 or 70 times threshold. In addition stimulating the nerves at 200 times threshold but at frequencies of 2 and 5 Hz significantly decreased total pulmonary resistance. The decrease in total pulmonary resistance evoked by electrically stimulating the nerves at 200 times threshold was unaffected by propranolol but was abolished by atropine methylnitrate. We conclude that stimulating group III and IV gracilis muscle afferents in dogs reflexly decreases total pulmonary resistance, an effect due to the withdrawal of a tonic cholinergic input to the airways.

Anatomical localization of the cells of origin of efferent fibers in the superior laryngeal and recurrent laryngeal nerves of the dogs

Using horseradish peroxidase, we identified the cells of origin of motor fibers in the superior laryngeal and recurrent laryngeal nerves of dogs. Cells giving rise to fibers in the superior laryngeal nerve were found in the dorsal motor nucleus and the nucleus ambiguus, whereas cells giving rise to fibers in the recurrent laryngeal nerve were found in the nucleus ambiguus and nucleus retroambigualis, but usually not in the dorsal motor nucleus.

Immunoneutralization of substance P attenuates the reflex pressor response to muscular contraction

We previously reported that subarachnoid injection of a peptide antagonist to substance P attenuated by half the reflex pressor response to static muscular contraction. Subsequently, some of the peptide antagonists to substance P have been found to possess local anesthetic effects. Therefore, we have repeated our experiments using a substance P antiserum, which was shown to be without local anesthetic effect. We found that intrathecal injection of the antiserum attenuated by more than half the reflex pressor response to static contraction of the triceps surae muscles of cats.

Occlusion of pressor responses to posterior diencephalic stimulation and muscular contraction.

Although neural occlusion has been suggested to occur between the central and reflex mechanisms increasing arterial pressure, evidence consistent with this phenomenon is lacking. To assess the possibility of neural occlusion we recorded, in chloralose-anesthetized cats, the pressor responses to statically contracting the hindlimb muscles and to electrically stimulating histologically confirmed sites in the posterior hypothalamus and subthalamus. We also recorded the pressor responses to topical application of capsaicin onto the intestine and to stimulation of these diencephalic sites. The pressor responses to simultaneous static contraction and diencephalic stimulation were significantly smaller than the algebraic sum of the pressor responses to contraction and diencephalic stimulation evoked separately. Likewise, the pressor responses to simultaneous capsaicin application and diencephalic stimulation were significantly smaller than the algebraic sum of the responses evoked separately. High intensity stimulation of the L7 dorsal root or the diencephalic sites evoked pressor responses similar in magnitude to the algebraic sum of the two responses evoked separately; thus, the inability of the simultaneous maneuvers to evoke pressor responses that summed algebraically was not due to the fact that they caused a maximal effect. Our findings are consistent with the hypothesis that neural occlusion occurs during stimulation of the posterior diencephalon and static muscular contraction.

Muscular contraction reflexly relaxes tracheal smooth muscle in dogs.

Although contraction of hindlimb skeletal muscle is well known to reflexly increase ventilation, heart rate and arterial pressure, little is known about the reflex effect of this maneuver on airway smooth muscle tone. Therefore, in chloralose-anesthetized dogs, we recorded transverse tension from the trachealis muscle while we contracted both gracilis muscles by electrically stimulating the gracilis nerves at 5 and 40 Hz. In 11 of the 13 dogs studied, static (40 Hz) contraction decreased tracheal tension, whereas in the remaining 2 dogs, static contraction increased tension. In 9 of 11 dogs, rhythmic (5 Hz) contraction decreased tracheal tension, whereas in the remaining 2, this maneuver increased tension. The changes in tracheal tension induced by stimulating the gracilis nerves were abolished by paralyzing the dogs and were restored, for the most part, after paralysis had dissipated. In addition, the contraction-induced changes in tension were not present when the gracilis muscles were contracted by stimulating the cut peripheral ends of the gracilis nerves. We conclude that muscular contraction reflexly relaxes tracheal smooth muscle in most dogs.

Attenuation of the reflex pressor response to muscular contraction by an antagonist to somatostatin.

Although group III and IV fibers are known to compose the afferent pathway of the reflex arc causing the pressor response to static muscular contraction, little is known about the neurotransmitters released by these muscle afferents. Somatostatin might be one of these neurotransmitters because this peptide is found in the terminals of fine afferent fibers ending in the dorsal horn of the lumbar spinal cord. Therefore, in chloralose-anesthetized cats, the reflex pressor response to static contraction was examined before and after subarachnoid injections onto the lumbosacral cord of a peptide antagonist to somatostatin. We found that before giving the antagonist, the pressor response to contraction of the triceps surae muscles in 12 cats averaged 33 ± 4 mm Hg, while 37 ± 7 minutes after giving the antagonist, the pressor response averaged only 18±3 nun Hg (p < 0.001). In contrast, the antagonist to somatostatin had no effect on either the pressor response to electrical stimulation of the cut central end of the sciatic nerve or the pressor response to stimulation of the posterior diencephalon. Furthermore, subarachnoid injection of a peptide antagonist to luteinlzing hormone-releasing hormone had no effect on the reflex pressor response to static contraction. Our findings are consistent with the hypothesis that somatostatin plays a role in the spinal transmission of the contraction-induced pressor reflex arising from hind limb skeletal muscle. (Circulation Research 1988;62:18-24)

Activation of visceral thin-fiber afferents increases respiratory output in cats

Respiratory responses to chemical activation of thin-fiber afferents from the stomach and the gallbladder were measured in anesthetized cats. Capsaicin or bradykinin applied to the serosal surface of either the stomach or the gallbladder elicited increases in breathing and phrenic nerve activity. Transection of the cervical vagi or the carotid sinus nerves had no effect on these responses. However, the respiratory responses to visceral stimulation were abolished by bilateral transection of the splanchnic nerves. We conclude that activation of thin-fiber afferents from the stomach and gallbladder causes a reflex increase in respiratory output. The initial afferent limb of this reflex is via the splanchnic nerves.

Atropine prevents the reflex tracheal relaxation arising from the stimulation of intestinal and skeletal muscle afferents in dogs

Using cholinergic and beta-adrenergic antagonists, we characterized the efferent arms of two reflex arcs that relax tracheal smooth muscle in dogs. The reflex arcs investigated were activated by the capsaicin-induced stimulation of afferent endings in the intestine and in the hindlimb. We found that the reflex tracheal relaxations were due to a withdrawal of a tonic cholinergic input. Beta-adrenergic pathways played little role in causing these reflex responses.