Distal Circular Muscle Research Articles

Esophageal anatomy and physiology vary across spastic and non-spastic phenotypes of disorders of esophagogastric junction outflow.

Pathophysiologic mechanisms of disorders of esophagogastric junction (EGJ) outflow are poorly understood. We aimed to compare anatomic and physiologic characteristics among patients with disorders of EGJ outflow and normal motility. We retrospectively evaluated adult patients with achalasia types 1, 2, 3, EGJ outflow obstruction (EGJOO) or normal motility on high-resolution manometry who underwent endoscopic ultrasound (EUS) from January 2019 to August 2022. Thickened circular muscle was defined as ≥1.6 mm. Characteristics from barium esophagram (BE) and functional lumen imaging probe (FLIP) were additionally assessed. Of 71 patients (mean age 56.2 years; 49% male), there were 8 (11%) normal motility, 58 (82%) had achalasia (5 (7%) type 1, 32 (45%) classic type 2, 21 (30%) type 3 [including 12 type 2 with FEPs]), and 7 (7%) had EGJOO. A significantly greater proportion of type 3 achalasia had thickened distal circular muscle (76.2%) versus normal motility (0%; p < 0.001) or type 2 achalasia (25%; p < 0.001). Type 1 achalasia had significantly wider mean maximum esophageal diameter on BE (57.8 mm) compared to type 2 achalasia (32.8 mm), type 3 achalasia (23.4 mm), EGJOO (15.9 mm), and normal motility (13.5 mm). 100% type 3 achalasia versus 0% type 1 achalasia/normal motility had tertiary contractions on BE. Mean EGJ distensibility index on FLIP was lower for type 3 achalasia (1.2 mmHg/mm2 ) and EGJOO (1.2 mmHg/mm2 ) versus type 2 (2.3 mmHg/mm2 ) and type 1 achalasia (2.9 mmHg/mm2 ). Our findings suggest distinct pathologic pathways may exist: type 3 achalasia and EGJOO may represent a spastic outflow phenotype consisting of a thickened, spastic circular muscle, which is distinct from type 1 and 2 achalasia consisting of a thin caliber circular muscle layer with more prominent esophageal dilation.

Mechanisms of cAMP-mediated relaxation of distal circular muscle in rabbit colon.

Photolytic release of free adenosine 3',5'-cyclic monophosphate (cAMP) from its caged form was used to evaluate the physiological role of several proposed mechanisms of cAMP-mediated relaxation of circular smooth muscle in the distal rabbit colon. Photolysis of caged cAMP produced a rapid relaxation of bethanechol-contracted distal circular muscle strips that was dependent on ultraviolet exposure time. An increase in release of free cAMP, associated with increased ultraviolet exposure, was confirmed with high-performance liquid chromatography. Vanadate (an ATPase inhibitor) (3 mM) caused a 48% decrease in cAMP-mediated relaxation, while ouabain and a zero K+ bath solution failed to affect relaxation. cAMP-mediated relaxation of KCl-contracted strips was significantly less effective than that of bethanechol-contracted strips. Although this finding suggested that cAMP-mediated relaxation may involve K+ channel modulation, specific (glibenclamide, charybdotoxin) and nonspecific (TEA) K+ channel blockade failed to affect cAMP-mediated relaxation of bethanechol-contracted strips. The photolytic release of cAMP failed to relax Ca(2+)-contracted saponin skinned muscle strips. These studies suggest 1) modulation of Ca2+ pumps plays an important role in this model of relaxation of distal colonic circular muscle in the rabbit colon, 2) modulation of the Na+ pump or sarcolemmal K+ channels may not play an important physiological role in relaxation induced by a rapid rise in intracellular cAMP, and 3) cAMP does not seem to have a significant physiological effect on the Ca2+ sensitivity contractile apparatus.

Effect of 5-hydroxytryptamine and its antagonists on colonic smooth muscle of the rabbit

The effect of 5-hydroxytryptamine (5HT) was studied in circular and longitudinal muscle from the proximal and distal colon of New Zealand white rabbits. 5HT stimulated a dose-dependent isometric contraction of distal and proximal circular muscle that was greater than in distal longitudinal muscle (P less than 0.01). 5HT did not stimulate taenia coli longitudinal muscle. The EC50 for 5HT stimulation of distal circular muscle (-7.0 +/- 0.1), distal longitudinal muscle, and proximal circular muscle was similar. Methysergide dose-dependently inhibited the 5HT stimulation of both proximal and distal circular muscle. The IC50 for methysergide inhibition of 5HT (5 x 10(-7) M) stimulation was -5.5 +/- 0.2. Ketanserine and ICS 205-930 did not inhibit 5HT stimulation of colonic muscle. Tetrodotoxin (TTX) decreased the potency, but not the efficacy of 5HT stimulation of proximal and distal circular muscle. Atropine decreased the potency (EC50 = -6.6 +/- 0.1) (P less than 0.05) and the efficacy by 40%. Electrical field stimulation (EFS) caused an on-contraction and off-contraction of distal circular muscle and an on-contraction of proximal circular muscle. 5HT decreased the off-contraction of the distal circular muscle but did not affect the on-contraction of the other muscle strips. 5HT receptor antagonists did not affect EFS of the tissue. The studies suggest: (1) 5HT stimulates circular colonic muscle with greater efficacy than longitudinal muscle, (2) 5HT stimulates circular muscle through a 5HT1 receptor, (3) there is atropine-sensitive and atropine-insensitive 5HT stimulation of circular colonic muscle, (4) 5HT inhibits neurons responsible for the off-contraction in distal circular muscle without affecting the on-contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Anatomic contribution to differences in rabbit colonic muscle contraction

The aim of this study was to determine if differences in the force of contraction in different regions of the rabbit colon are associated with variations in the histology of the corresponding muscle tissues. Circular and longitudinal muscles were isolated from strips of proximal and distal colonic muscle. Muscle strips stretched to L0 were either stimulated to contract or were processed for electron microscopy. Cross-sections of the smooth muscle cells of the taenia coli had a larger perimeter (P < 0.001) and were surrounded by increased extracellular matrix (28% of the standardized box) compared with the muscle cells from the other sites in the colon (7%–13%) (P < 0.001). Cross-sections of the proximal circular muscle cells had a smaller perimeter and were present in a greater number than the cells from other areas of the colon. The distal circular muscle generated a larger force than the other muscles after stimulation with bethanechol or K+ (P < 0.05). The taenia developed less force than the other muscles (P < 0.05). Bethanechol was a less potent stimulant for the longitudinal muscles than for the circular muscles (P < 0.05). This study suggests that (1) the decreased efficacy of bethanechol and K+ stimulation of the taenia coli is caused in part by the smaller number of cells that are available to contract and (2) the increased efficacy for the stimulation of the distal circular muscle compared with the proximal circular muscle is unrelated to the mass of muscle and seems to be related to an inherent property of the muscle.

Response of Smooth Muscle from Proximal and Distal Human Colon

Regional differences in colonic motility may be responsible for the orderly transit of intraluminal contents through the colon. The aims of this study were to compare the effect of stretch on active and passive stress development in colonic muscle from the proximal and distal colon and to compare the responses of these tissues to KC1 or bethanechol stimulation. Strips of taenia or circular smooth muscle were obtained from the disease‐free segment of the colon removed for adenocarcinoma. Passive, active, and total isometric stress were measured on full‐thickness strips of circular or longitudinal taenial muscle stimulated with bethanechol (10−4 M) as the muscles were stretched to 120% of the length of optimum tension (Lo.) The tissues then were stimulated with increasing concentrations of KCI and bethanechol while being stretched at Lo. The active stress in the proximal circular muscle was greater at all levels of stretch than in distal circular or longitudinal muscle (p &lt;.001). The resting and passive stress were greater in distal circular and longitudinal taenial muscle than in proximal circular muscle (p &lt; .05). There was a dose‐dependent increase in stress development to bethanechol and KCl in each type of muscle. Proximal circular muscle had the greatest response. The EDSO was shifted to the right in distal circular muscle (2.6 ± 0.1 × 10−5 M) compared to proximal circular muscle (1.1 ± 0.1 × 10−5 M) (p &lt; .001). These studies suggest that muscle stress differs in different locations of the colon and the role of active and passive stress development must be considered in models explaining in vivo colonic motility disturbances.

Neuropeptide responses and mechanics of the proximal and distal feline colon in vitro

Mechanical properties and responses to neuropeptides were compared for proximal and distal feline colonic muscle. Proximal longitudinal (PL), proximal circular (PC), distal longitudinal (DL), and distal circular (DC) muscles were studied in vitro under isometric conditions. Total tension in DL [1.636 +/- 0.009 (SE) kg/cm2] was greater than in DC (0.699 +/- 0.004 kg/cm2) or PC (0.710 +/- 0.005 kg/cm2, P less than 0.05). Longitudinal muscle developed proportionately more active tension than circular muscle at each region (80.9% in DL vs. 54.1% in DC and 77.1% in PL vs. 52.3% in PC, P less than 0.01). Neuropeptides varied in potency and efficacy. Cholecystokinin octapeptide (CCK-8) was the most potent and efficacious in PL and substance P was the most efficacious in PC muscle (P less than 0.05). Substance P was more efficacious whereas CCK-8 and neurotensin were less efficacious in PC than PL muscle (P less than 0.01). DL muscle did not respond to CCK-8. DC muscle did not respond to CCK-8 or neurotensin. Isometric contractions to each neuropeptide were insensitive to tetrodotoxin. We conclude that 1) mechanical properties of circular and longitudinal colonic muscle differ and 2) responses to neuropeptides depend on anatomic region and intrinsic properties.

Effect of Cholinergic Agonists on Muscle From Rodent Proximal and Distal Small Intestine

Proximal and distal rat small intestine was cut into strips measuring 6.0 X 10.0 mm. Strips cut along the oral-caudal axis were called longitudinal strips, whereas those cut 90 degrees to that axis were called circular strips. Stress in circular and longitudinal muscle strips was measured continuously as they were superfused with acetylcholine, carbamylcholine, methacholine, bethanechol, or physostigmine. Resting stress during stretch, acetylcholine-stimulated active stress, and total stress were determined. Proximal circular muscle was five times as sensitive to acetylcholine as distal circular muscle (p less than 0.05); proximal longitudinal muscle was 2.8 times as sensitive to bethanechol as distal muscle (p less than 0.05). Resting, active, and total stress were similar in proximal and distal muscle, but circular muscle showed nearly twice the resting stress of longitudinal muscle at either proximal or distal sites (p less than 0.05). Physostigmine (10(-6) M) increased acetylcholine-stimulated active stress in proximal and distal circular muscle by 29% and 70%, respectively (p less than 0.05), but not in longitudinal muscle (p greater than 0.05). This difference between proximal and distal circular muscle (41%) was also significant (p less than 0.05). Thus, the proximal and distal muscle of the rat small intestine differs in its sensitivity to various cholinergic agonists, but not in its length-stress properties.