An experimental analysis of mechanisms engaged in reflex inhibition of intestinal motility.

Abstract

Summary The present study was performed with the aim of investigating what mechanisms are employed in eliciting the reflexly induced inhibition of intestinal motility, and thus how the central inhibitory control of intestinal motility is brought about. The following four essentially different modes of action were considered: 1 A centrally controlled specific inhibitory innervation of the intestinal smooth muscles. 2 An ‘overflow’ of the vasoconstrictor fibre transmitter, inducing an inhibitory action on adjacent intestinal smooth muscle cells. 3 A shift in the local chemical environment of the intestinal smooth muscle, secondary to the reduction in blood supply brought about by sympathetic vasoconstrictor activity. 4 An increased secretion of catechol amines from the adrenal medulla, induced by splanchnic nerve fibre activation and reaching the intestinal smooth muscle cells by way of the blood stream. The experiments were performed on acutely vagotomized, anaesthetized cats and arranged so that intestinal motility could be recorded in a jejunal loop in situ. The blood pressure and the intestinal blood flow were also recorded. In order to induce reflex excitations of the sympatho-adrenal system the experimental animals were exposed to occlusion of the carotid arteries, graded withdrawal of blood, and electrical or mechanical stimulation of thin afferent fibres in somatic nerves. In the course of these procedures for inducing reflex inhibition of the intestinal motility, the effects of exclusion of the adrenal secretion and of denervation of the intestinal segment on intestinal motility and blood flow were studied. The reflexly induced responses were also quantitatively compared with the effects obtained by electrical stimulations of the splanchnic nerves, with or without exclusion of the adrenal glands, and with the intestino-intestinal inhibitory reflex. Further, the inhibitory effects on intestinal motility of intravenous infusion of catechol amines were studied and, lastly, graded reductions of the intestinal blood supply were mechanically induced. It was found that the inhibitory responses induced by carotid occlusion, by withdrawal of blood and by stimulation of afferent somatic nerves were not noticeably affected by denervation of the intestine. In practically no case, however, could inhibitory responses be obtained after adrenalectomy, or when the venous blood from the adrenal glands was diverted from the general circulation. By re-infusion of the adrenal venous blood thus collected, an intestinal inhibition appeared which was essentially identical with that obtained when the adrenal circulation was intact. As long as the adrenal glands were intact, direct splanchnic stimulation induced an almost maximal intestinal inhibition at frequencies as low as 1—2 impulses per second. The latency of the onset of this inhibition corresponded to the circulation time from the adrenal glands to the intestine. Contrary to this delayed, but pronounced inhibitory response, the intestinal vasoconstriction was always prompt. The inhibitory responses obtained by stimulation of the splanchnic nerves with low frequencies could be prevented by exclusion of the adrenal glands, and they thus appear to be almost entirely a result of the activation of the adrenal medullary cells. After exclusion of the adrenal glands, splanchnic stimulation still induced a prompt and undiminished vasoconstrictor response; but in general it was now necessary to use frequencies above 8–10 impulses per second to induce any significant intestinal inhibition. There are strong reasons for believing that this inhibitory response to high frequency stimulation is partly a consequence of an ‘overflow’ of the transmitter substance at the vasoconstrictor nerve endings, and partly due to the now marked reduction in intestinal blood supply induced by the intestinal vasoconstrictor fibres. In striking contrast to the delayed intestinal inhibition, seen on direct stimulation of the splanchnic nerves at ‘physiological’ frequencies or on reflex sympathetic activation, a prompt and intense intestinal inhibition occurred regularly on distension of another, isolated part of the intestine, even when the splanchnic nerves had been cut. The rapidity of the onset of this intestino-intestinal inhibitory reflex had all the characteristics of a direct neurogenic mechanism, and it was first abolished when the nerve ramifications along the mesenteric vessels were destroyed. This purely local reflex does not appear to be influenced by any centrally controlled sympathetic nerve fibres. It thus seems that, under normal circumstances, centrally induced inhibition of intestinal motility is practically exclusively dependent on the hormonal component of the sympatho-adrenal system.