Indirect stimulation by thyrotropin-releasing hormone of canine gallbladder motility

Thyrotropin-releasing hormone (TRH) was unable to induce any noticeable contraction of canine isolated gallbladder strips up to the dose of 10(-4) g/ml, while caerulein (CAER) was spasmogenic in a dose-related manner beyond 10(-11) g/ml. This effect of CAER was unaffected by either atropine or tetrodotoxin. In conscious dogs, the intravenous bolus of TRH (20 micrograms/kg) or CAER (0.2-2.0 micrograms/kg) caused gallbladder emptying. The TRH response, unlike that of an equipotent dose of CAER, was prevented by atropine. In experiments on electrical activity of the digestive tract in conscious dogs, both TRH or CAER induced a concomitant increase on the myoelectrical activity in the proximal part of the small intestine. The excitatory effects were prevented by atropine only in the case of TRH. These results demonstrate that TRH stimulates indirectly the gallbladder and proximal duodenum of the dog. They suggest the involvement of a cholinergic pathway in this excitatory action.     

Postpubertal changes in the histomorphometric characteristics of the uterus of the indigenous West African pig

The epithelial height and myometrial and endometrial characteristics of the fundus, corpus and neck regions of the uteri of 28 virgin West African indigenous gilts in four age groups (6-8, 10-12, 16-18 and 20-22 months) were histometrically evaluated. Though regionally stable, the height of luminal epithelial cells was, respectively, reduced and enhanced in the fundus and neck regions by 10-12 months. The myometrium was thinner in the fundus and was severely reduced in the corpus region in gilts aged 16-18 months. Contrarily, the endometrium was regionally stable in thickness but underwent some thickening in the corpus of 16 to 18-month-old gilts. The respective occurrence of muscular and glandular tissues in the myometrium and endometrium was regionally influenced while older gilts had more circular muscles than the others. Generally, over 70% of the glands and 60% of the muscles were complex glands and longitudinal muscles, respectively. Results depict the nonuniform growth rates of different uterine tissues in the different regions and suggest that the improvement in the litter-carrying capacity of the uterus in these pigs continues well after puberty.     

Influence of PGF2 alpha on gastrointestinal activity in the conscious piglet.

In 5 conscious piglets with electrodes implanted on the antrum pylori, duodenum, jejunum and ileum, the effect of intravenous infusion of PGF2 alpha, 1 and 10 micrograms/kg/min during 2 h, on gastrointestinal electrical activity was studied. The influence of the PG, 10(-8) to 10(-4) M, on longitudinal tissue strips from the same segments was also examined. The in vitro results demonstrate that PGF2 alpha has only a weak contractile effect on duodenal and jejunal strips. This effect was enhanced in the presence of atropine and indomethacin. In the in vivo part of the study PGF2 alpha induced an inhibition of antral electrical activity as evidenced by a prolongation of the inhibitory phases and a reduction of the frequency of the fast oscillations. In the small intestine only ileal activity was changed significantly. PGF2 alpha provoked an increase in the phase II or irregular spiking activity and an increase in the interval of the migrating myoelectrical complexes in this segment.     

Prostaglandin E2 formation by rat gastroduodenal tissue following intragastric acid perfusion

Rat gastroduodenal mucosa forms prostaglandin (PG) E2. However, little is known about regional differences in PGE2 formation or the effect of gastric hydrochloric acid (HC1) perfusion on regional PGE2 formation. In this study, the rats were divided into 3 groups. Group 1 received intravenous (i.v.), 1 Ml/h, and intragastric (i.g.), 8 ml/h, perfusions of saline simultaneously for 3 h. Group 2 received saline i.v. and 0.15 N HC1 i.g., 8 ml/h. Group 3 was injected with a bolus of asprin (ASA), 60 mg/kg, followed by ASA, 40 mg/kg/h i.v., and 0.15 N HC1 i.g.. The gastric aspirates were analyzed for volume and pH. Segments of gastroduodenal tissue from the fundus, corpus, antrum, and duodenum were minced and then incubated in 1 ml of 5 mM Tris buffer, pH 8.4, for 30 sec with mixing; the incubate was assayed for PGE2 by radioimmunoassay. Intragastric HC1 decreased the pH of aspirate without producing gastric mucosal lesions. However, when combined with i.v. ASA, ulcer formation was present in all animals (p less than 0.05). PGE2 was formed by isolated tissue from four different gastroduodenal regions. The duodenum formed significantly greater amounts than the fundus, antrum, or corpus, which were similar. Intragastric HC1 produced a trend toward increased PGE2 formation (pmol PGE2/mg tissue) in the fundus, 143 +/- 36 to 237 +/- 57; corpus, 87 +/- 13 to 200 +/- 57; antrum, 157 +/- 28 to 224 +/- 65; and duodenum, 235 +/- 56 to 338 +/- 51. However, statistical significance was not reached.     

Effect of cholecystokinin octapeptide and somatostatin on the motility of guinea pig and canine gallbladder

Species differences have been observed in the effect of cholecystokinin octapeptide (CCK OP) on the canine and guinea pig gallbladder smooth muscle motility. 1. CCK OP was more potent stimulant in canine than in guinea pig gallbladder smooth muscles. Its pD2 values were 10 and 9.2, respectively. 2. The acetylcholine (10(-4) M)-induced maximum contractions in canine gallbladder muscle strips were by 50% lower as compared to the CCK OP (10(-8) M) maximum responses while in guinea pig gallbladder muscle strips the acetylcholine (ACh) maximum responses were by 20% lower than the CCK OP maximum responses. 3. CCK OP increased [3H]ACh release by 27% in canine gallbladder and by 40% in guinea pig gallbladder. 4. Somatostatin (SOM) had not any direct myogenic effect in guinea pig and canine gallbladder but it decreased [3H]ACh release from gallbladder intrinsic cholinergic neurons.     

Hepatic cholesterol metabolism in cholesterol gallstone disease

Hepatic cholesterol metabolism was examined in 27 Swedish patients with cholesterol gallstone disease and in 13 patients free of gallstones operated for roentgenographically suspect polyps in the gallbladder. All 40 patients underwent cholecystectomy, and a liver biopsy and gallbladder bile were obtained at surgery. The cholesterol saturation of gallbladder bile was significantly higher in patients with gallstones compared to the gallstone-free controls (131 +/- 13 vs. 75 +/- 5%, P less than 0.001). Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, governing cholesterol synthesis, did not differ between gallstone and gallstone-free patients (104 +/- 11 vs. and 109 +/- 22 pmol/min per mg protein, respectively). The activity of cholesterol 7 alpha-hydroxylase, catalyzing the catabolism of cholesterol to bile acids, was not significantly decreased in gallstone patients (6.2 +/- 1.1 vs. 8.0 +/- 2.0 pmol/min per mg protein). The capacity to esterify cholesterol, judged by the activity of acyl coenzyme A:cholesterol acyltransferase (ACAT), was similar in gallstone and gallstone-free patients (5.4 +/- 0.4 vs. 6.7 +/- 1.1 pmol/min per mg protein). In the presence of exogenous cholesterol, ACAT activity increased by more than fourfold in both groups. No correlation was found between the saturation of gallbladder bile and any of the mentioned enzyme activities in gallstone patients. It is concluded that distinct abnormalities in cholesterol metabolizing enzymes are not of major importance for development of gallstones in Swedish patients with cholesterol gallstone disease. The results support the contention that the etiology of cholesterol gallstones is multifactorial.     

The effect of vasoactive intestinal polypeptide (VIP) on the canine gallbladder motility.

1. VIP at doses of 10(-9) to 10(-8) M was ineffective and at doses of 5 x 10(-8) to 10(-7) M exerted a slight inhibitory effect on the tone of the canine gallbladder muscle strip. However, VIP (0.1-1 micrograms/kg) injected intravenously (i.v.) in conscious dogs dose-dependently decreased the gallbladder pressure. 2. VIP did not influence significantly the acetylcholine (ACh)- or carbachol- induced contractions of canine gallbladder under in vitro or in vivo conditions, but it decreased the electrically-induced, atropine-sensitive contractions of gallbladder muscle strips. 3. VIP (5 x 10(-9) to 5 x 10(-8) M) did not influence significantly the dose-response curve for cholecystokinin octapeptide (CCK OP) of canine and guinea-pig gallbladder muscle strips. VIP injected i.v. (0.1-0.5 micrograms/kg) in conscious dogs greatly decreased the CCK OP-induced gallbladder pressure.     

Pituitary adenylate cyclase activating polypeptide stimulates gallbladder motility in conscious dogs.

We investigated whether pituitary adenylate cyclase activating polypeptide (PA-CAP27 and PACAP38) had any effect on gallbladder motility in conscious dogs, in which force transducers were chronically implanted in the gastric antrum, duodenum and gallbladder. PACAP27 and PACAP38 were administered intravenously during the digestive and interdigestive states at doses of 30, 100 and 300 pmol/kg. By way of comparison, cholecystokinin octapeptide (CCK-OP) was administrated at doses of 3, 9 and 27 pmol/kg. As a result, each peptide evoked transient and tonic contractions both in the digestive and interdigestive states, and the effect on the motor index was dose dependent. PACAP27 and PACAP38 were 0.11 +/- 0.03 and 0.04 +/- 0.01 as potent as CCK-OP in the digestive state, and 0.18 +/- 0.04 and 0.02 +/- 0.01 in the interdigestive state, respectively, on a molar basis. Although PACAP27 and PACAP38 belong to the vasoactive intestinal polypeptide (VIP) family, intravenous administration of 300 pmol/kg of VIP had no effect on interdigestive gallbladder motility, but on the other hand inhibited gallbladder motility in the digestive state. The contractile effects of PACAP27 and PACAP38 were almost completely abolished by pretreatment with atropine or hexamethonium, but not with L364718. An in vitro study using canine gallbladder strips showed that PACAP27 and PACAP38 had no effect on spontaneous gallbladder motor activity evoked by electric field stimulation, CCK-OP or acetylcholine. It was concluded that PACAP27 and PACAP38 stimulate gallbladder motility in conscious dogs through a preganglionic cholinergic mechanism.     

Comparison of the biological activity of canine and porcine motilin in rabbit

The biological activity of porcine and canine motilin was studied in rabbits by establishing dose-response curves of both peptides using two different methods. The dissociation constant, obtained from the displacement of iodinated porcine motilin by canine motilin was 0.6 +/- 0.3 nM, versus 1.2 +/- 0.4 nM for porcine motilin. For the 13-norleucine and 13-leucine analogues of porcine motilin a value of 0.8 +/- 0.3 nM was obtained. Both motilins were almost equipotent in stimulating the in vitro contractile response of longitudinal smooth muscle strips: half-maximal effect was achieved at a concentration of 1.0 +/- 0.1 nM for canine versus 1.3 +/- 0.2 nM for the 13-norleucine analogue of porcine motilin. We conclude that porcine and canine motilin have a comparable bioactivity in the rabbit, although canine motilin is slightly more effective. The motilin receptor is probably specific for the N-terminal portion which is identical in both molecules.     

Stomach stress and strain depend on location, direction and the layered structure

The stomach is as other parts of the gastrointestinal tract functionally subjected to dimensional change. Hence, the biomechanical properties are of functional importance. Our group has previously demonstrated that the stress–strain properties of the rat and rabbit stomach wall were species-, location- and direction-dependent. We further wanted to study the anisotropic biomechanical properties of the stomach wall in pigs. Furthermore, we made an in-depth biomechanical test on the layered wall of the stomach in different regions. Two stomach strips were cut both in longitudinal direction (parallel with the greater curvature) and circumferential direction (perpendicular to the greater curvature) from the gastric fundus, corpus and antrum. One strip was used for the non-separated (intact) wall test and the other one was separated for the test on the mucosa–submucosa and muscle layers individually. The length, thickness and width of each strip were measured from digital images. The uni-axial stress and strain were computed from the force generation and the tissue strip deformation during stretching. The muscle layer was the thickest in the antrum whereas the mucosal–submucosal layer was the thickest in the corpus of the stomach (P<0.01). The strips from the corpus were stiffest among the three regions in both longitudinal and circumferential directions (P<0.001). The longitudinal strips was stiffer than the circumferential strips in all three regions (P<0.001) and the mucosa–submucosa strips was stiffer than the intact wall and the muscle layer in both directions for the fundus and the corpus (P<0.001). The constant a of the intact wall and mucosa–submucosa layer was in both directions linearly associated with the mucosa–submucosa thickness. In conclusion, the uni-axial stress–strain curves of pig stomach were location-, direction- and layer-dependent. The stiffer wall in the corpus is likely due to its thicker mucosa, i.e., the stiffness of the mucosa–submucosa layer seems can explain the intact wall stiffness. Since the structure and function of the pig stomach are similar to the human stomach, we believe that the data obtained from this study can be extended to humans. Detailed biomechanical mapping of the stomach will likely help us to understand physiological functions of the different parts of the human stomach, such as gastric accommodation and mechanosensation.     

Permeability properties of the subepithelial tissues of Necturus gallbladder

The permeability properties of the subepithelial connective tissue of Necturus gallbladder were evaluated by measurement of electrical resistance, dilution potentials and hydraulic water permeability. The gallbladder epithelial cells were removed by scraping and the underlying connective tissue placed in an Ussing chamber. The electrical resistance was 2.2 +/- 0.8 omega X cm2; the tissue was slightly cation selective relative to free solution. The subepithelial tissues restricted the rate of diffusion of small solutes to 50% of the free solution value. The hydraulic water permeability averaged 2.1 X 10(-2) cm/s per atm. We conclude that limitations of the area of subepithelium available for fluid movement are the most important factors in determining the restrictions to solute and water flow offered by the subepithelial tissues.     

Half life of gastrointestinal glucagon-like immunoreactive materials.

The composition, half life and hyperglycemic action of the porcine gastrointestinal glucagon-like immunoreactive materials were examined. Glucagon immunoreactivity (GI) measured using specific antiglucagon serum was more abundunt in the extract from the gastric fundus than in the one from the small intestine. When the extract from the gastric fundus was injected in dogs, the half life (T1/2) of total glucagon-like immunoreactivity (total GLI) measured using nonspecific antiglucagon serum was 9.5 +/- 1.1 min (mean +/- SEM), which was longer than that of crystalline pancreatic glucagon, 3.4 +/- 0.2 min, but shorter than that of the extract from the small intestine, 15.9 +/- 1.3 min. On the other hand, T1/2 for GI from the gastric fundus was 5.1 +/- 0.9 min, which was not significantly different from that of crystalline pancreatic glucagon. Blood sugar levels were significantly increased from the basal by 25 +/- 4 mg/100 ml at 10 min and 19 +/- 4 mg/100 ml at 15 min following an injection of the extract from the gastric fundus, but such a change in blood sugar levels was not demonstrated when the extract from the small intestine was injected. These results suggest that GI of the gastric fundus is close to pancreatic glucagon in respect of its metabolism and hyperglycemic activity.     

Interruption of the enterohepatic circulation of bile acids stimulates the esterification rate of cholesterol in human liver.

The activity of acyl CoA: cholesterol acyltransferase (ACAT), which catalyzes the esterification of cholesterol, was studied in liver microsomes obtained from cholestyramine-treated gallstone patients (n = 12) and patients with Crohn's disease who had undergone partial ileal resection (n = 11). Gallstone patients (n = 33) and gallstone-free subjects undergoing cholecystectomy because of polyps of the gallbladder (n = 8) served as controls. The mean levels of the ACAT activity were the same in the gallstone and the gallstone-free patient groups (6.0 +/- 0.4 and 6.1 +/- 1.1 pmol/min per mg protein, respectively). When exogenous cholesterol was added to the assay system the activities were increased four- to fivefold in both groups. The ACAT activity tended to be increased in the cholestyramine-treated patients (8.1 +/- 1.8 pmol/min per mg protein), and was significantly enhanced (P less than 0.005) in the ileal-resected patients (12.3 +/- 2.3 pmol/min per mg protein). When the enzyme activity was determined with added exogenous cholesterol, it was significantly higher compared to the controls in both the cholestyramine-treated patients and the patients with ileal resection (57.9 +/- 11.6 and 50.0 +/- 10.3 pmol/min per mg protein, respectively). The content of free and esterified cholesterol in liver homogenates and microsomes was not significantly different between the patient groups. We conclude that ACAT activity is increased in patients with interruption of the enterohepatic circulation of bile acids, and speculate that this reflects a stimulated uptake of lipoprotein cholesterol and may indicate that more cholesteryl esters are incorporated into very low density lipoproteins.     

Tumor necrosis factor production and accumulation of inflammatory cells in the corpus luteum of pseudopregnancy and pregnancy in rabbits

The potential involvement of macrophages, T lymphocytes, and the cytokine tumor necrosis factor (TNF) in regression of the corpus luteum was investigated at different stages of pseudopregnancy and pregnancy by use of immunocytochemical methods and a TNF bioassay. Few macrophages (11 +/- 6 per high power field of 8-microns frozen sections of corpus luteum, Day 10 of pseudopregnancy) were observed until the very end of pseudopregnancy, when the number of macrophages increased greatly (176 +/- 42 per high power field, Day 19 of pseudopregnancy). Pregnancy, of 32 days duration, delayed large-scale macrophage accumulation until 3 days after parturition (154 +/- 30 per high power field). Low TNF activity (approximately 1.0 U/mg protein) was detected in incubations of luteal tissue at all stages; in response to lipopolysaccharide, TNF values in medium increased 10- to 30-fold at times of luteal regression and macrophage accumulation (1 day postpartum and Day 19 of pseudopregnancy). Class II-positive T lymphocytes were observed in luteal tissue, but unlike macrophages, the number of lymphocytes did not increase at the time of regression of the corpus luteum. These data are consistent with the hypothesis that involution of the corpus luteum is promoted through the interactions of inflammatory cells and action of TNF, although the action of TNF has not been determined in this luteal tissue. Through unknown mechanisms, pregnancy postpones the accumulation of macrophages in the corpus luteum, in association with the prolongation of luteal function until the time of parturition.     

Differential responses of regional sympathetic activity and blood flow to visceral afferent stimulation

The sympathetic nervous system is essential for the cardiovascular responses to stimulation of visceral afferents. It remains unclear how the reflex-evoked sympathetic output is distributed to different vascular beds to initiate the hemodynamic changes. In the present study, we examined changes in regional sympathetic nerve activity and blood flows in anesthetized cats. Cardiovascular reflexes were induced by either electrical stimulation of the right splanchnic nerve or application of 10 microg/ml of bradykinin to the gallbladder. Blood flows were measured using colored microspheres or the Transonic flow meter system. Sympathetic efferent activity was recorded from the left splanchnic, inferior cardiac, and tibial nerves. Stimulation of visceral afferents decreased significantly blood flows in the celiac (from 49 +/- 4 to 25 +/- 3 ml/min) and superior mesenteric (from 35 +/- 4 to 23 +/- 2 ml/min) arteries, and the vascular resistance in the splanchnic bed was profoundly increased. Consistently, stimulation of visceral afferents decreased tissue blood flows in the splanchnic organs. By contrast, activation of visceral afferents increased significantly blood flows in the coronary artery and portal vein but did not alter the vascular resistance of the femoral artery. Furthermore, stimulation of visceral afferents increased significantly sympathetic efferent activity in the splanchnic (182 +/- 44%) but not in the inferior cardiac and tibial nerves. Therefore, this study provides substantial new evidence that stimulation of abdominal visceral afferents differentially induces sympathetic outflow to the splanchnic vascular bed.     

Ovine fetal electrocortical activity and regional cerebral blood flow

Fetuses of 12 near-term sheep were prepared for microsphere determination of cerebral blood flow. Experiments were performed 5 days postsurgery. The regional blood flows were measured in successive high (HV), low (LV) and high voltage electrocorticographic states. Comparisons were made between the observations made in the LV and averaged flanking HV cycles. Total cerebral blood flow was 95 +/- 8, 119 +/- 11 and 100 +/- 9 ml/min/100 g in HV, LV and HV, respectively. Low voltage electrocortical activity increased average cerebral blood flow by 22% (P less than 0.01). Significant changes were seen in all regions except the occipital cortex. The maximum change was observed in the thalamus in which the flows were 152 +/- 23, 243 +/- 35 and 138 +/- 20 ml/min/per 100 g tissue, respectively. The increase was 68% (P less than 0.001). The percent changes seen in the cerebrum are as follows: Frontal grey + 18%, frontal white + 22%, parietal white + 22%, temporal + 18%. A + 17% change was seen in the cord (P less than 0.03). It is concluded that in low voltage electrocortical activity all of the brain, except the occipital region, shows an increase in cerebral blood flow. This is probably secondary to a variance in cerebral activity. This preparation may be useful in localizing function in the fetal brain.     

Influence of carbachol and isoproterenol on myoelectrical activity of the uterus, vagina, and duodenum in the conscious domestic hen

The influence of intravenous infusion (20 min) of carbachol (CAR) and isoproterenol (IPN) on myoelectrical activity of the uterus, vagina, and duodenum was studied in 6 conscious and unrestrained hens. IPN infusions (1.5, 7.5, and 15 micrograms/hen/min) were performed before oviposition, and CAR infusions (0.5, 1.5, and 5 micrograms/hen/min) were administered after oviposition. CAR infusions resulted in a significant stimulation of myoelectrical activity of the vagina (1.5 and 5 micrograms/min) and the duodenum (5 micrograms/min), and in a significant increase (45 +/- 6%) in heart rate (HR), as compared to control values. These effects were blocked by previous i.v. injections of atropine (0.4 mg/hen). IPN infusions induced a significant inhibition of myoelectrical activity of the middle (7.5 and 15 micrograms/min) and caudal (all doses) uterine segments, of the vagina (7.5 and 15 micrograms/min), and of the duodenum (15 micrograms/min), and a significant tachycardia (39 +/- 14%) as compared to control values. The inhibitory effects of IPN on all organs studied and the stimulatory action on HR were suppressed by propranolol (0.24 mg/hen). The sensitivity of the vagina to both drugs argues for a more active participation of this oviductal part in the mechanism of oviposition.     

Subregional and Intracellular Distribution of NADP-Linked Malic Enzyme in Human Brain

High total activity (expressed as μmol/min/g of wet tissue or per milligram of DNA) and differential subregional distribution of NADP-linked malic enzyme was found in autopsy specimens of human brain. Striatum showed the highest activity of malic enzyme, which was two to five-fold higher than that in other human organs tested. High activity was also found in frontal cortex, while the lowest activity of the enzyme in the central nervous system was found in cerebellum, substantia alba, and corpus callosum. In striatum, frontal cortex, pens, and cerebellum more than 80% of total malic enzyme activity was localized in the mitochondrial fraction, while in substantia alba and corpus callosum approximately 60% of the enzyme activity was present in the mitochondrial fraction. Relatively high specific activity of malic enzyme was found in a crude mitochondrial fraction isolated from various regions of human brain. The highest specific activity was found in the mitochondria isolated from striatum (more than 100 nmol/min/mg of mitochondrial protein); the lowest, but still high (approximately 32 nmol/min/mg of mitochondrial protein) was present in corpus callosum. These data and the different ratios of citrate synthase to mitochondrial malic enzyme activities found in different regions of brain suggest that human brain mitochondria, like the mitochondria isolated from other mammalian brains, are extremely heterogenous. A possible role of mitochondrial malic enzyme in human brain metabolism is discussed.     

Effect of CCK-8 on myoelectrical activity of the gastrointestinal tract in the conscious miniature pig

In conscious miniature pigs, with implanted electrodes in the wall of the antrum pylori, duodenum, jejunum, and ileum, the influence of IV infusions of CCK-8 (17.5 and 175 pM/kg/min) on gastrointestinal myoelectrical activity was measured. Although both doses under study induced a decrease in antral spike activity, only the higher dose resulted in an overall decrease in integrated myoelectrical activity. In the ileum both doses augmented spiking activity during the infusion, but inhibited electrical activity after the end of the infusion. No response was observed in the duodenum and jejunum. The experiments demonstrate the overall inhibitory effect of CCK-8 on antral electrical activity and its stimulatory influence on ileal smooth muscle.     

Influence of vestibular activation on respiration in humans

The purpose of this study was to determine the effects of the semicircular canals and otolith organs on respiration in humans. On the basis of animal studies, we hypothesized that vestibular activation would elicit a vestibulorespiratory reflex. To test this hypothesis, respiratory measures, arterial blood pressure, and heart rate were measured during engagement of semicircular canals and/or otolith organs. Dynamic upright pitch and roll (15 cycles/min), which activate the otolith organs and semicircular canals, increased respiratory rate (Delta2 +/- 1 and Delta3 +/- 1 breaths/min, respectively; P < 0.05). Dynamic yaw and lateral pitch (15 cycles/min), which activate the semicircular canals, increased respiration similarly (Delta3 +/- 1 and Delta2 +/- 1, respectively; P < 0.05). Dynamic chair rotation (15 cycles/min), which mimics dynamic yaw but eliminates neck muscle afferent, increased respiration (Delta3 +/- 1; P < 0.05) comparable to dynamic yaw (15 cycles/min). Increases in respiratory rate were graded as greater responses occurred during upright (Delta5 +/- 2 breaths/min) and lateral pitch (Delta4 +/- 1) and roll (Delta5 +/- 1) performed at 30 cycles/min. Increases in breathing frequency resulted in increases in minute ventilation during most interventions. Static head-down rotation, which activates otolith organs, did not alter respiratory rate (Delta1 +/- 1 breaths/min). Collectively, these data indicate that semicircular canals, but not otolith organs or neck muscle afferents, mediate increased ventilation in humans and support the concept that vestibular activation alters respiration in humans.