J. C. Longhurst

Effects of capsaicin and bradykinin on afferent fibers with ending in skeletal muscle.

Capsaicin, injected into the arterial supply of the skinned hindlimb of dogs, evokes reflex increases in cardiovascular function. Moreover, the cardiovascular reflexes evoked by capsaicin are very similar to those evoked by static exercise. The afferent fibers initiating these reflex increases have not been identified electrophysiologically, although their endings are believed to be located in skeletal muscle. We have, therefore, attempted to determine which afferent fibers are stimulated by capsaicin. In anesthetized dogs, we recorded impulses from afferent fibers with endings in either the gastrocnemius or gracilis muscles and injected capsaicin (10–30 μg/kg) into the abdominal aorta. Capsaicin stimulated 24 of 34 group IV (C fiber) endings, but only 5 of 19 group III (Aδ fiber) endings. By contrast, bradykinin (0.5–1.5 μg/kg) stimulated 17 of 33 group IV endings and 9 of 19 group III endings. Impulse activity for the 24 group IV afferents stimulated by capsaicin increased from 0.7 ± 0.1 to a peak of 9.3 ± 1.4 imp/sec. Firing started 6 ± 1 seconds after injection and remained above control levels for 24 ± 5 seconds. Capsaicin had no significant effect on the firing rate of 30 group I and II muscle afferents. Our results suggest that group IV muscle afferents are primarily responsible for causing the reflex increases in cardiovascular function evoked by injecting capsaicin into the arterial supply of the skinned hindlimb of dogs. Moreover, capsaicin is likely to be a useful pharmacological tool with which to determine the reflex autonomic effects caused by stimulation of group IV muscle afferents.

Cardiovascular reflexes resulting from capsaicin-stimulated gastric receptors in anesthetized dogs.

To determine whether significant cardiovascular reflexes can be generated from gastric receptor stimulation, we developed an autoperfused canine stomach preparation from a dog anesthetized with a-chloralose so that capsaicin, a C fiber agonist, could be injected into the left gastroepiploic artery (ia) supplying the greater curvature of the stomach. Control injections were made into the inferior vena cava (IVC) to determine capsaicins effects on areas downstream from the stomach. Significant cardiovascular reflexes were obtained in 37 of 42 dogs after ia injection and in 26 of 26 dogs after IVC injection. Capsaicin (25-500 jig) caused significant increases in systolic blood pressure (SBP) (15%), heart rate (HR) (4%), contractility (maximal dP/dt) (19%), and systemic vascular resistance (SVR) (18%), whereas there were no changes in left ventricular end-diastolic pressure (LVEDP) or aortic flow (AF). On the other hand, downstream IVC capsaicin injections caused significant decreases in SBP (28%), HR (34%), dP/dt (33%), and AF (41%), but no change in SVR or LVEDP. The dP/dt response to ia injection continued to occur after overdrive right atrial pacing. However, the responses of pressure, rate, and dP/dt were diminished to a large extent by diaphragmatic celiac nerve section and to a smaller extent by diaphragmatic vagus nerve section. We conclude that these results demonstrate that capsaicin, a potent C-fiber agonist, can stimulate gastric or perigastric receptors to induce a significant activation of the cardiovascular system. Thus, the potential of the stomach to function as a reflexogenic organ which regulates the cardiovascular system has been demonstrated. Circ Res 46: 780-788, 1980

Reflex alpha-adrenergic coronary vasoconstriction during hindlimb static exercise in dogs.

We studied 18 α-chloralose-anesthetized dogs to determine if α-adrenergic coronary vasoconstriction occurs with hindlimb static exercise. Exercise was elicited by spinal cord ventral nerve root stimulation.