The Evidence that Adrenal Secretion Is Increased in Emotional Excitement
That blood from the adrenal veins causes the relaxation of intestinal muscle characteristic of adrenal extract or adrenin is shown in [Fig. 3]. The muscle was originally beating in blood which contained no demonstrable amount of adrenal secretion; this inactive blood was replaced by blood from the adrenal veins, obtained after quick etherization. Etherization, it will be recalled, is accompanied by a “stage of excitement.” Relaxation occurred almost immediately (at b). Then the rhythm was renewed in the former blood, and thereupon the muscle was surrounded with blood from the vein leading away from the left kidney, i. e., blood obtained from the same animal and under the same conditions as the adrenal blood, but from a neighboring vein. No relaxation occurred. By this and other similar tests the reliability of the method was proved.
Figure 3.—Intestinal muscle beating in inactive blood, which was withdrawn from the chamber at a. Blood from the adrenal vein of an animal excited by etherization was substituted at b, and withdrawn at c. Contractions were restored in the original inactive blood which was removed at d. Blood from the renal vein (same animal) was added at e.
In this and subsequent records time is marked in half minutes.
In no instance did blood from the inferior vena cava of the quiet normal animal produce relaxation. On the other hand, blood from the animal after emotional excitement showed more or less promptly the typical relaxation. In [Fig. 4] is represented the record of intestinal muscle which was beating regularly in Ringer’s solution. At a the Ringer’s solution was removed, and at b “excited” blood was added; after the preliminary shortening, which, as already stated, occurs at the first immersion in blood, the muscle lengthened gradually into complete inhibition. At c the “excited” blood was removed, and at d “quiet” blood was added in its place. The muscle at once began fairly regular rhythmic beats. At e the “quiet” blood was removed, and at f the “excited” blood was again applied. The muscle lengthened almost immediately into an inhibited state. In this instance the “excited” blood was taken after the cat had been barked at for about fifteen minutes.
Figure 4.—Alternate application of “excited” blood (at b and f) and “quiet” blood (at d), from the same animal, to intestinal muscle initially beating in Ringer’s solution.
The increase of effect with prolongation of the period of excitement is shown in [Fig. 5]. A is the record of contractions after the muscle was surrounded with “quiet” blood serum. B shows the gradual inhibition which occurred when the muscle was surrounded with defibrinated blood taken when the animal had been excited eleven minutes. And C is the record of rapid inhibition after fifteen minutes of excitement. In other instances the effect was manifested merely by a lowering of the tonus of the muscle, and a notable slowing of the beats, without, however, a total abolition of them.
Figure 5.—The effect of prolonging the excitement. A, the record in “quiet” serum; B, in defibrinated blood after eleven minutes of excitement; and C, in serum after fifteen minutes of excitement.
The inference that this inhibition of contraction of the intestinal muscle is due to an increased amount of adrenal secretion in the “excited” blood de la Paz and I justified on several grounds:
(1) The inhibition was produced by “excited” blood from the inferior vena cava anterior to the mouths of the adrenal veins, when blood from the femoral vein, taken at the same time, had no inhibitory influence. Since blood from the femoral vein is typical of the cava blood below the entrance of the kidney veins, the conclusion is warranted that the difference of effect of the two samples of blood is not due to any agent below the kidneys. But that blood from the kidneys does not cause the relaxation is shown in [Fig. 3]. The only other structures which could alter the blood between the two points at which it was taken are the adrenal glands, and the material secreted by them would produce precisely the inhibition of contraction which was in fact produced.
(2) If in ether anesthesia the blood vessels leading to and from the adrenal glands are first carefully tied, and then the glands are removed, excitement four or five hours later, before the weakness that follows the removal has become prominent, does not alter the blood so that the typical inhibition occurs (see [Fig. 6]). Thus, although the animal shows all the characteristic signs of sympathetic stimulation, the blood, in the absence of the adrenals, remains unchanged.
Figure 6.—Failure of the cava blood (added at a) to produce inhibition when excitement has occurred after removal of the adrenal glands. The muscle later proved sensitive to adrenin in blood in the ratio 1:1,000,000.
(3) As already shown, sometimes the effect produced by the “excited” blood was prompt inhibition, sometimes the inhibition followed only after several beats, and sometimes a slowing and shortening of contractions, with a lower tone, were the sole signs of the action of adrenin. All these degrees of relaxation can be duplicated by adding to inactive blood varying amounts of adrenin. [Fig. 7] shows the effects, on a somewhat insensitive muscle preparation, of adding adrenin, 1:1,000,000 (A), 1:2,000,000 (B), and 1:3,000,000 (C), to different samples of blood previously without inhibitory influence. These effects of adrenin and the effects produced by blood taken near the opening of the adrenal veins are strikingly analogous.
Figure 7.—Effect of adding adrenin 1:1,000,000 (A), 1:2,000,000 (B), and 1:3,000,000 (C), to formerly inactive blood. In each case a marks the moment when the quiet blood was removed, and b, the time when the blood with adrenin was added.
(4) Embden and v. Furth[1] have reported that 0.1 gram of suprarenin chloride disappears almost completely in two hours if added to 200 cubic centimeters of defibrinated beef blood, and the mixture constantly aerated at body temperature. “Excited” blood which produces inhibition loses that power on standing in the cold for twenty-four hours, or on being kept warm and agitated with bubbling oxygen. This change is illustrated in [Fig. 8]; the power of the “excited” blood to inhibit the contractions of the intestinal muscle when record A was written was destroyed after three hours of exposure to bubbling oxygen, as shown by record B. The destruction of adrenin and the disappearance of the effect which adrenin would produce are thus closely parallel.
Figure 8.—The effect of bubbling oxygen through active blood. A, relaxation after active blood applied at a; B, failure of relaxation when the same blood, oxygenated three hours, was applied to a fresh strip at b.
All these considerations, taken with the proof that sympathetic impulses increase secretion of the adrenal glands, and taken also with the evidence that, during such emotional excitement as was employed in these experiments, signs of sympathetic discharges appeared throughout the animal from the dilated pupil of the eye to the standing hairs of the tail-tip, led us to the conclusions that the characteristic action of adrenin on intestinal muscle was in fact, in our experiments, due to secretion of the adrenal glands, and that that secretion is increased in great emotion.