Gut Blood Flow Research Articles

Clinical management of constipation – the role of physical activity - systematic review

Constipation is a prevalent gastrointestinal disorder that affects a significant portion of the global population, yet its management remains challenging due to its complex etiology. This review explores the potential benefits and mechanisms of physical activity in alleviating constipation symptoms. We examined recent studies on the physiological effects of various exercise types and intensities on bowel movements, gastrointestinal blood flow, and microbiome composition. Our findings suggest that aerobic exercise enhances colonic motility and accelerates gastrointestinal transit, though the effects vary depending on exercise duration and intensity. While light to moderate physical activity (less than 60 minutes) appears beneficial, prolonged or intense exercise may inhibit motility and exacerbate symptoms. Additionally, exercise-induced changes in the gut microbiome and blood flow dynamics were observed, influencing stool consistency and colonic function. However, the interplay between diet, hydration, and physical activity is crucial, as adequate dietary fiber and hydration are essential for optimizing exercise's impact on constipation. Although evidence supports the role of physical activity in managing constipation, further research is needed to clarify the most effective exercise regimens and their integration with dietary and lifestyle modifications.

Measuring gut perfusion and blood flow in neonates using ultrasound Doppler of the superior mesenteric artery: a narrative review.

The gut is a relatively silent organ in utero but takes on a major role after birth for the absorption and digestion of feed for adequate nutrition and growth. The neonatal circulation undergoes a transition period after birth, and gut perfusion increases rapidly to satisfy the oxygen demand and consumption. If this process is compromised at any stage, preterm and fetal growth restricted infants are at particular risk of gut tissue injury secondary to hypoxia, leading to necrotizing enterocolitis. Feeding can also be a challenge in these high-risk groups due to gut dysmotility. Superior mesenteric artery (SMA) Doppler is a safe, bedside investigation that could rapidly aid clinicians with feeding strategies and in monitoring high-risk infants. This article aims to establish normal patterns of gut blood flow velocity in neonates using SMA Doppler and reviews how it might be used clinically in pathologic states.

In vivo phenotyping of the microvasculature in necrotizing enterocolitis with multicontrast optical imaging.

Necrotizing enterocolitis (NEC) is the most prevalent gastrointestinal emergency in premature infants and is characterized by a dysfunctional gut microcirculation. Therefore, there is a dire need for in vivo methods to characterize NEC-induced changes in the structure and function of the gut microcirculation, that is, its vascular phenotype. Since in vivo gut imaging methods are often slow and employ a single-contrast mechanism, we developed a rapid multicontrast imaging technique and a novel analyses pipeline for phenotyping the gut microcirculation. Using an experimental NEC model, we acquired in vivo images of the gut microvasculature and blood flow over a 5000 × 7000 μm2 field of view at 5μm resolution via the following two endogenous contrast mechanisms: intrinsic optical signals and laser speckles. Next, we transformed intestinal images into rectilinear "flat maps," and delineated 1A/V gut microvessels and their perfusion territories as "intestinal vascular units" (IVUs). Employing IVUs, we quantified and visualized NEC-induced changes to the gut vascular phenotype. In vivo imaging required 60-100s per animal. Relative to the healthy gut, NEC intestines showed a significant overall decrease (i.e. 64-72%) in perfusion, accompanied by vasoconstriction (i.e. 9-12%) and a reduction in perfusion entropy (19%)within sections of the vascular bed. Multicontrast imaging coupled with IVU-based in vivo vascular phenotyping is a powerful new tool for elucidating NEC pathogenesis.

Energetic savings and cardiovascular dynamics of a marine euryhaline fish (Myoxocephalus scorpius) in reduced salinity

Few studies have addressed how reduced water salinity affects cardiovascular and metabolic function in marine euryhaline fishes, despite its relevance for predicting impacts of natural salinity variations and ongoing climate change on marine fish populations. Here, shorthorn sculpin (Myoxocephalus scorpius) were subjected to different durations of reduced water salinity from 33 to 15 ppt. Routine metabolic rate decreased after short-term acclimation (4–9 days) to 15 ppt, which corresponded with similar reductions in cardiac output. Likewise, standard metabolic rate decreased after acute transition (3 h) from 33 to 15 ppt, suggesting a reduced energetic cost of osmoregulation at 15 ppt. Interestingly, gut blood flow remained unchanged across salinities, which contrasts with previous findings in freshwater euryhaline teleosts (e.g., rainbow trout) exposed to different salinities. Although plasma osmolality, [Na+], [Cl−] and [Ca2+] decreased in 15 ppt, there were no signs of cellular osmotic stress as plasma [K+], [hemoglobin] and hematocrit remained unchanged. Taken together, our data suggest that shorthorn sculpin are relatively weak plasma osmoregulators that apply a strategy whereby epithelial ion transport mechanisms are partially maintained across salinities, while plasma composition is allowed to fluctuate within certain ranges. This may have energetic benefits in environments where salinity naturally fluctuates, and could provide shorthorn sculpin with competitive advantages if salinity fluctuations intensify with climate change in the future.

Role of Transient Receptor Potential Ankyrin‐1 (TRPA1) in Endothelial‐Specific Effects of Diverse Aldehydes

IntroductionStructurally diverse aldehydes are found in abundance in the environment including in foods, beverages and tobacco‐derived aerosols. Some aldehydes are associated with cardiovascular disease risk especially in cigarettes smokers, however, the detailed mechanisms by which aldehydes influence cardiovascular health and disease are incompletely known.ObjectiveBecause reactive aldehydes, in general, are considered instigators of endothelium dysfunction, we explored the direct effects of a diverse set of aldehydes in isolated murine blood vessels, i.e., aorta and superior mesenteric artery (SMA).MethodsAldehydes: acetaldehyde (AA); formaldehyde (FA); cinnamaldehyde (CA); crotonaldehyde (CR); and a TRPA1 agonist, allyl isothiocyanate (AITC, mustard oil), were tested for vascular effects in isolated murine aorta and SMA using isometric myography.ResultsAll aldehydes induced endothelium‐dependent relaxation in SMA. AA (1–100 mM), FA (30–1,500 μM), CA (30–300 μM) and CR (1–100 μM) strongly and reversibly relaxed (>75% relaxation) agonist‐induced contractions. High levels of FA (1.2–1.6 mM) and CR (>300 μM) irreversibly altered vascular function in aorta and SMA. To identify the mechanism of aldehyde‐induced relaxations, isolated blood vessels were pre‐contracted with phenylephrine (PE), U46,619 (thromboxane A2 analog), or 60 mM K+ (High K) and then exposed to AA, FA, CA, CR or AITC with intact or mechanically‐impaired endothelium (air‐perfused) as well as in the absence or presence of: 1) Nω‐Nitro‐L‐arginine methyl ester hydrochloride (L‐NAME); 2) an inhibitor of guanylyl cyclase (ODQ); and, 3) a TRPA1 antagonist (A967079; 1 μM). The sensitivity (EC50) but not the efficacy (% decreased tension) of FA‐ and AA‐induced relaxations was dependent on the contractile agonist (i.e., PE < U46,619 ≤ High K) indicating multiple mechanisms. In PE pre‐contracted SMA, vasorelaxations at the lowest levels of AA, FA, CA, CR and AITC were inhibited significantly by mechanically‐disrupted endothelium, L‐NAME, ODQ, and by TRPA1 antagonist except for AA, which was TRPA1 independent. TRPA1 was co‐localized with isolectin immunofluorescent staining in SMA endothelium but not in aorta.ConclusionBecause low levels (physiological) of several aldehydes (FA, CA, CR) induce reversible and efficacious vasorelaxations via TRPA1 channels, we propose that endogenous and exogenous sources of these aldehydes may significantly impact gut (mesenteric) blood flow to augment postprandial hyperemia in aid of digestion and nutrient uptake.Support or Funding InformationResearch funding from the National Institutes of Health: GM127607, HL122676, U54HL120163.

Postprandial Vascular Dysfunction Is Associated With Raised Blood Pressure and Adverse Left Ventricular Remodeling in Adolescent Adiposity.

Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular disease, including heart failure. Although linked to obesity and hypertension, its pathogenesis is multifactorial. Blunted postprandial sympathetic regulation of gut blood flow has been observed in overweight animals and suggested as a promotor of hypertension and LVH. We hypothesized that blunted postprandial superior mesenteric blood flow responses would be more common in overweight humans and associated with increased blood pressure and LVH. Left ventricular dimensions and hemodynamic responses to a standardized high-calorie liquid meal were measured in healthy adolescents (n=82; 39 overweight/obese) by magnetic resonance imaging. Covariates such as body mass index, blood pressure, Tanner score, and an index of insulin resistance were included in multiple regression models to examine the independent associations of mesenteric flow response with blood pressure status and LVH. Food ingestion increased cardiac output (Δmean, 0.45 [SD, 0.62] L·min-1; P=3.8×10-8) and superior mesenteric artery flow (Δmean, 0.76 [SD, 0.35] L·min-1; P=4.2×10-31). A blunted mesenteric flow response was associated with increased left ventricular mass (B=-12.7 g·m-2.7 per L·min-1·m-0.92; P=6×10-5) and concentric LVH (log likelihood, -9.9; P=0.001), independently of known determinants of LVH, including body mass index. It was also associated with elevated systolic blood pressure (B=-18.0 mm Hg per L·min-1·m-0.92; P=0.001), but this link did not explain the association with left ventricular mass. Postprandial mesenteric vascular dysfunction is associated with LVH and hypertension, independently of common risk factors for those conditions. These findings highlight a new, independent marker of cardiovascular risk in the young.

Effect of Oral Feeding on Gastric Emptying, Gut Blood Flow, and Hormone Responses in Obese and Healthy Weight Subjects

Effect of Oral Feeding on Gastric Emptying, Gut Blood Flow, and Hormone Responses in Obese and Healthy Weight Subjects

Exertional Heat Stroke: Pathophysiology, Epidemiology, Diagnosis, Treatment, and Prevention.

Temperature increases due to climate changes and operations expected to be conducted in hot environments make heat-related injuries a major medical concern for the military. The most serious of heat-related injuries is exertional heat stroke (EHS). EHS generally occurs when health individual perform physical activity in hot environments and the balance between body heat production and heat dissipation is upset resulting in excessive body heat storage. Blood flow to the skin is increased to assist in dissipating heat while gut blood flow is considerably reduced, and this increases the permeability of the gastrointestinal mucosa. Toxic materials from gut bacteria leak through the gastrointestinal mucosa into the central circulation triggering an inflammatory response, disseminated intravascular coagulation (DIC), multiorgan failure, and vascular collapse. In addition, high heat directly damages cellular proteins resulting in cellular death. In the United States military, the overall incidence of clinically diagnosed heat stroke from 1998 to 2017 was (mean ± standard deviation) 2.7 ± 0.5 cases/10,000 Soldier-years and outpatient rates rose over this period. The cornerstone of EHS diagnosis is recognition of central nervous dysfunction (ataxia, loss of balance, convulsions, irrational behavior, unusual behavior, inappropriate comments, collapse, and loss of consciousness) and a body core temperature (obtained with a rectal thermometer) usually >40.5°C (105°F). The gold standard treatment is whole body cold water immersion. In the field where water immersion is not available it may be necessary to use ice packs or very cold, wet towels placed over as much of the body as possible before transportation of the victim to higher levels of medical care. The key to prevention of EHS and other heat-related injuries is proper heat acclimation, understanding work/rest cycles, proper hydration during activity, and assuring that physical activity is matched to the Soldiers' fitness levels. Also, certain dietary supplements (DSs) may have effects on energy expenditure, gastrointestinal function, and thermoregulation that should be considered and understood. In many cases over-motivation is a major risk factor. Commanders and trainers should be alert to any change in the Soldier's behavior. Proper attention to these factors should considerably reduce the incidence of EHS.

In vivo aerobic metabolism of the rainbow trout gut and the effects of an acute temperature increase and stress event.

The fish gut is responsible for numerous potentially energetically costly processes, yet little is known about its metabolism. Here, we provide the first in vivo measurements of aerobic metabolism of the gut in a teleost fish by measuring gut blood flow, as well as arterial and portal venous oxygen content. At 10°C, gut oxygen uptake rate was 4.3±0.5 ml O2h-1kg-1 (∼11% of whole-animal oxygen uptake). Following acute warming to 15°C, gut blood flow increased ∼3.4-fold and gut oxygen uptake rate increased ∼3.7-fold (16.0±3.3 ml O2h-1kg-1), now representing ∼25% of whole-animal oxygen uptake. Although gut blood flow decreased following an acute stress event at 15°C, gut oxygen uptake remained unchanged as a result of a ∼2-fold increase in oxygen extraction. The high metabolic thermal sensitivity of the gut could have important implications for the overall aerobic capacity and performance of fish in a warming world and warrants further investigation.

Taurine Protects Gut Barrier Function and Prevents Endothelial Cell Injury Induced by Ischaemia-Reperfusion

Purpose: Gut permeability and microvascular injury following ischaemia/reperfusion (IR) have been implicated in the systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF). Taurine (TAU), a sulfur-containing amino acid, is a powerful antioxidant and regulator of intracellular calcium and several studies have established that treatment with TAU protects cerebral, cardiac and testicular tissue from (IR) injury. This study investigates the protective effect of taurine in an experimental model of I/R-induced gut injury in rats. Methods: Sprague-Dawley rats were randomized into three groups: Control, I/R, TAU + I/R. TAU was given by gavage or intravenous injection before I/R. Ischaemia was induced by cross-clamping superior mesenteric and coeliac vascular pedicle for 20 - 30 min, followed by 60 - 180 min reperfusion. Gut permeability, blood flux, tissue oedema, leucocytes infiltration and eNOS expression were measured at 3 hrs following reperfusion using FD4. Leukocyte-endothelial interactions were determined by intra-vital microscopy during I/R. In vitro studies assessed the protective effect of TAU on endothelial cell function and survival. Results: Treatment with TAU significantly attenuated IR-induced gut hyper permeability, tissue oedema, leukocyte adhesion and infiltration. TAU also prevented the reduction in gut blood flow, leukocyte rolling velocity and eNOS expression induced by IR. TAU protects against I/R-induced endothelial cell injury by reduced anti-oxidant activity and modulation of eNOS expression and intracellular calcium fluxes. Conclusions: TAU protects the gut from intestinal barrier dysfunction induced by surgical I/R.

Pharmacologic Stress Gastropathy Prophylaxis May Not Be Necessary in At-Risk Surgical Trauma ICU Patients Tolerating Enteral Nutrition.

Stress gastropathy is a rare complication of the intensive care unit stay with high morbidity and mortality. There are data that support the concept that patients tolerating enteral nutrition have sufficient gut blood flow to obviate the need for prophylaxis; however, no robust studies exist. This study assesses the incidence of clinically significant gastrointestinal bleeding in surgical trauma intensive care unit (STICU) patients at risk of stress gastropathy secondary to mechanical ventilation receiving enteral nutrition without pharmacologic prophylaxis. A retrospective cohort study of records from 2008 to 2013. Adult patients in a single-center STICU were included. Patients were included if they received full enteral nutrition while on mechanical ventilation. Exclusion criteria were coagulopathy, glucocorticoid use, prior-to-admission acid-suppressive therapy use, direct trauma or surgery to the stomach, failure to tolerate goal enteral nutrition, orders to allow natural death, and deviation from the intervention. Pharmacologic stress ulcer prophylaxis was discontinued once enteral nutrition was providing full caloric requirements for patients requiring mechanical ventilation. A total of 200 patients were included. The median age was 42 years, 83.0% were male, and 96.0% were trauma patients. The incidence of clinically significant gastrointestinal bleeding was 0.50%, with a subset analysis of traumatic brain injury patients yielding an incidence of 0.68%. Rates of ventilator-associated pneumonia and Clostridium difficile infection were low at 1.0 case/1000 ventilator days and 0.2 events/1000 patient days, respectively. Hospital all-cause mortality was 2.0%. Cost savings of US$121/patient stay were realized. Stress gastropathy is rare in this population. Surgical and trauma patients at risk for stress gastropathy did not benefit from continued pharmacologic prophylaxis once they tolerated enteral nutrition. Pharmacologic prophylaxis may safely be discontinued in this patient population. Further investigation is warranted to determine whether continued prophylaxis after attaining enteral feeding goals is detrimental.

Effects of acute temperature changes on gut physiology in two species of sculpin from the west coast of Greenland

For a fish to thrive, the gut must function efficiently. This is achieved through a range of processes, including controlled patterns of gut motility and modifications in gut blood flow. The knowledge of how gut functions in fish are affected by environmental temperature is sparse, and in order to understand how changes in climate may affect fish populations, we need to understand how gut blood flow and gut motility are affected by changes in temperature. By simultaneous recording of gut blood flow, gut motility, cardiac output, heart rate and cardiac stroke volume, in vivo at 4, 9 and 14 °C, the acute thermal sensitivity of a thermal generalist (shorthorn sculpin Myoxocephalu scorpius) was compared to the more strictly Arctic species (Arctic sculpin M. scorpioides). Temperature effects on gut motility were further explored in vitro, using isolated smooth muscles. Elevated water temperatures increased gut blood flow and contractile activity. Contraction frequency increased nearly threefold and gut blood flow almost doubled with the 10 °C increase. Both cardiac output and heart rate increased with temperature, while cardiac stroke volume decreased. The cholinergic agonist carbachol was most potent on smooth muscles at 9 °C. There were no differences between the two species, suggesting that the gastrointestinal and cardiovascular systems of Arctic sculpin, although a more pronounced Arctic species, have similar abilities to cope with acute fluctuations in water temperature as shorthorn sculpin. The impact of increased gut activity at higher temperatures needs further investigation before the effects of climate change can be predicted.

Effect of thoracic epidural anaesthesia on splanchnic blood flow

Thoracic epidural anaesthesia (TEA) is used widely in colorectal surgery. However, there is increasing concern that epidurals are associated with postoperative hypotension, mediating a potential reduction in splanchnic flow. The aim was to review the literature on the effects of TEA on splanchnic blood flow. PubMed and Cochrane databases were searched. Search terms used were: English language, 'thoracic epidural splanchnic flow', 'thoracic epidural gut blood flow', 'thoracic epidural intestinal blood flow' and 'thoracic epidural colonic blood flow'. Abstracts were reviewed by two independent researchers and irrelevant studies excluded. The full text of the remaining articles was then retrieved. Twenty-two abstracts were reviewed and three excluded. Nineteen papers were reviewed in full and seven irrelevant articles excluded. Five human studies investigated the effects of TEA on splanchnic flow. Two studies measured splanchnic flow directly and found an epidural-mediated fall in flow, unresponsive to intravenous fluids and requiring vasopressors or inotropes to restore baseline flow. The remaining three studies had inconsistent findings and haemodynamic stability was maintained. The seven animal studies identified were heterogeneous in both methodology and findings. Three suggested a protective role for thoracic epidurals in septic shock and pancreatitis. These findings are inconsistent; however, the two studies that investigated the effects of vasoconstrictors on splanchnic blood flow directly both found a significant epidural-mediated reduction in splanchnic blood flow that was unresponsive to fluid therapy.

Effects of feeding on thermoregulatory behaviours and gut blood flow in white sturgeon (Acipenser transmontanus) using biotelemetry in combination with standard techniques

The effects of thermoregulatory behaviours on gut blood flow in white sturgeon Acipenser transmontanus before and after feeding was studied using a blood flow biotelemetry system in combination with a temperature preference chamber. This is the first study to look at cardiovascular responses to feeding in white sturgeon, and also the first time behavioural tests in fish have been combined with recordings of cardiac output, heart rate, cardiac stroke volume and gut blood flow. The results showed strong correlations between gut blood flow and temperature choice after feeding (R(2)=0.88+/-0.03, 6-8 h postprandially and R(2)=0.89+/-0.04, 8-10 h postprandially) but not prior to feeding (R(2)=0.11+/-0.05). Feeding did not affect the actual temperature preference (18.4+/-0.7 degrees C before feeding, 18.1+/-0.7 degrees C, 6-8 h postprandially and 17.5+/-0.5 degrees C, 8-10 h postprandially). Fish instrumented with a blood flow biotelemetry device, and allowed to move freely in the water, had a significantly lower resting heart rate (37.3+/-0.26 beats min(-1)) compared with the control group that was traditionally instrumented with transit-time blood flow probes and kept in a confined area in accordance with the standard procedure (43.2+/-2.1 beats min(-1)). This study shows, for the first time in fish, the correlation between body temperature and gut blood flow during behavioural thermoregulation.

Mechanisms of nitric oxide-mediated, neurogenic vasodilation in mesenteric resistance arteries of toad Bufo marinus

This study determined the role of nitric oxide (NO) in neurogenic vasodilation in mesenteric resistance arteries of the toad Bufo marinus. NO synthase (NOS) was anatomically demonstrated in perivascular nerves, but not in the endothelium. ACh and nicotine caused TTX-sensitive neurogenic vasodilation of mesenteric arteries. The ACh-induced vasodilation was endothelium-independent and was mediated by the NO/soluble guanylyl cyclase signaling pathway, inasmuch as the vasodilation was blocked by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and the NOS inhibitors N(omega)-nitro-l-arginine methyl ester and N(omega)-nitro-l-arginine. Furthermore, the ACh-induced vasodilation was significantly decreased by the more selective neural NOS inhibitor N(5)-(1-imino-3-butenyl)-l-ornithine. The nicotine-induced vasodilation was endothelium-independent and mediated by NO and calcitonin gene-related peptide (CGRP), inasmuch as pretreatment of mesenteric arteries with a combination of N(omega)-nitro-l-arginine and the CGRP receptor antagonist CGRP-(8-37) blocked the vasodilation. Clotrimazole significantly decreased the ACh-induced response, providing evidence that a component of the NO vasodilation involved Ca(2+)-activated K(+) or voltage-gated K(+) channels. These data show that NO control of mesenteric resistance arteries of toad is provided by nitrergic nerves, rather than the endothelium, and implicate NO as a potentially important regulator of gut blood flow and peripheral blood pressure.

The participation of the sympathetic innervation of the gastrointestinal tract in disease states

Knowledge of neural circuits, neurotransmitters and receptors involved in the sympathetic regulation of gastrointestinal (GI) function is well established. However, it is only recently that the interaction of sympathetic neurons, and of sympathetic transmitters, with the GI immune system and with gut flora has begun to be explored. Changes in the behaviour of sympathetic nerves when gut function is compromised, for example in ileus and in inflammation, have been observed, but the roles of the sympathetic innervation in these and other pathologies are not adequately understood. In this article, we first review the principal roles of the sympathetic innervation of the GI tract in controlling motility, fluid exchange and gut blood flow in healthy individuals. We then discuss the evidence that there are important interactions of sympathetic transmitters with the gut immune system and enteric glia, and evidence that inflammation has substantial effects on sympathetic neurons. These reciprocal interactions contribute to pathological changes in ways that are not yet clarified. Finally, we focus on inflammation, diabetes and postoperative ileus as conditions in which there is sympathetic involvement in compromised gut function.

Postprandial changes in enteric electrical activity and gut blood flow in rainbow trout (Oncorhynchus mykiss) acclimated to different temperatures

Enteric electrical activity, cardiac output and gut blood flow were measured in rainbow trout (Oncorhynchus mykiss) acclimated to either 10 degrees C or 16 degrees C. Enteric electrical activity showed, in both the fasted and postprandial state, a distinct pattern with clusters of burst-like events interspersed by silent periods. The frequency of electrical events increased postprandially for both acclimation groups. Event frequency increased from 3.0+/-0.5 to 9.6+/-1.4 events min(-1) and from 5.9+/-0.9 to 11.8+/-2.0 events min(-1) in the 10 degrees C and 16 degrees C groups, respectively. Similarly, the number of events per cluster increased postprandially for both acclimation groups. Gut blood flow, cardiac output and heart rate increased after feeding. The gut blood flow significantly increased in both groups and peaked at 257+/-19% and 236+/-22% in the 10 degrees C and 16 degrees C groups, respectively. There was a strong correlation between the number of events and gut blood flow at both temperatures. Comparison between the two groups showed that fish acclimated to 16 degrees C may have an increased cost of sustaining the basal activity of the gut compared with the group acclimated to 10 degrees C. In conclusion, we have for the first time measured enteric electrical activity in vivo in a fish species and we have also demonstrated a strong correlation between gut blood flow and enteric electrical activity in fasted and postprandial fish.

ENOS signaling is essential in GLP‐2‐mediated stimulation of blood flow, but not cell proliferation in the mouse gut

Through a G protein‐coupled receptor, glucagon‐like peptide‐2 (GLP‐2) stimulates intestinal crypt cell proliferation and mucosal blood flow. GLP‐2 receptor is localized to enteric neurons, endocrine cells, and myofibroblasts, but not enterocytes. However, it is largely unknown how GLP‐2 receptor‐activated mitogenic, cytoprotective, and vasoactive signals are conveyed to the intestinal epithelium. Nitric oxide can function as a cellular signal to regulate cell growth and blood flow. Thus, our objective was to determine whether nitric oxide is a key mediator in the GLP‐2 receptor‐activated enteric signaling network. Endothelial nitric oxide synthase knockout (eNOS KO) and wild‐type (eNOS WT) mice (n=40) were subcutaneously injected with GLP‐2 or saline for 14 d, and with BrdU 2 h prior to euthanization. Mucosal cell proliferation, apoptosis, and blood flow were determined by BrdU‐positive cells, active caspase‐3 abundance, and hemoglobin (Hb) content, respectively. There was no difference between eNOS KO and WT mice in gut growth (indicated by mucosal weight, protein mass, villous height and crypt depth), cell proliferation, apoptosis, or blood flow. GLP‐2 increased gut growth by stimulating crypt cell proliferation in both KO and WT mice. GLP‐2 appeared to decrease apoptosis in the WT mice, but increase it in the KO mice. Importantly, GLP‐2 increased gut blood flow in the WT mice, but not in the KO mice. We conclude that GLP‐2‐induced vasoactive action is mediated by the eNOS signaling, but GLP‐2‐stimulated tropic action is independent of it. (Supported by USDA CRIS 6250‐51000‐043 and NIDDK K01DK75489)

Nutrient-induced gastrointestinal hyperemia and specific dynamic action in rainbow trout (Oncorhynchus mykiss)—importance of proteins and lipids

Mechanical gastric distension induces a dorsal aortic pressor response in rainbow trout (Oncorhynchus mykiss) with no change in gastrointestinal blood flow. To elucidate what role chemical stimuli from the digested food has on the postprandial cardiovascular response, a new method was developed to investigate the contribution of individual nutrient components. Three predigested experimental diets were injected directly into the proximal intestine of rainbow trout and cardiac output (CO), gut blood flow (Qcma), heart rate (HR), and stroke volume (SV) were recorded. Specific dynamic action (SDA) was estimated by measuring oxygen consumption. When a balanced diet (50% protein, 25% fat, 15% carbohydrate) was injected, Qcma and CO increased within 1 h by 45 and 27%, respectively. The response to a high-protein diet (70% protein, 5% fat, 15% carbohydrate) was quantitatively similar but delayed, with a maximal blood flow response after 2 h. With a high-lipid diet (60% fat, 15% protein, 15% carbohydrate), the peak increase in Qcma by 22% occurred after 30 min and thereafter declined rapidly. The SDA response (19%) to the balanced diet was temporally matched with the hyperemia. With a high-protein diet, the response is delayed and enlarged (34%) compared with the balanced diet. The high-lipid diet gave no significant SDA response. We conclude that the chemical composition of the food influences the postprandial hyperemia and the SDA, such that the components appear to work in a synergistic fashion. The present results also demonstrate that both redistribution of blood flow and an overall increase in CO contribute to the postprandial increase in gut blood flow in this species.

Effects of gastric distension and feeding on cardiovascular variables in the shorthorn sculpin (Myoxocephalus scorpius)

We have previously shown in rainbow trout (Oncorhynchus mykiss) that gastric distension induces an instantaneous alpha-adrenoceptor-mediated increase in the dorsal aortic blood pressure (P(da)), with no change in cardiac output (CO), gut blood flow (Q(cma)), or heart rate. To investigate if feeding habits affect these patterns and to compare the differences between gastric distension alone and feeding in the same experimental setting, we used the short-horn sculpin (Myoxocephalus scorpius), an inactive ambush predator with a capacity to eat large meals. An inflatable balloon was placed in the stomach of one group while another group was fed fish meat. When distending the stomach with a volume corresponding to a meal of 8-10% body weight, there is a profound and long-lasting increase in systemic (123 +/- 27%) and gastrointestinal (R(cma); 82 +/- 24%) vascular resistance, leading to an increase in P(da) (19%) without any change in CO or Q(cma). After force-feeding, there is a rapid transient increase in R(cma) (24 +/- 4%) and an even larger P(da) response (53%). There is also a subsequent increase in both CO (28 +/- 8%) and Q(cma) (27 +/- 9%) after 30 min. By 15 h, CO and Q(cma) increase further (41 +/- 11 and 63 +/- 14%, respectively), and this increase persists for up to 60 h. The increase in Q(cma) is mediated via both an increase in CO and a shunting of blood from the systemic circulation via a decrease in R(cma) (34 +/- 7%). In conclusion, the response to mechanical distension of the stomach is similar to what we have described in rainbow trout, and the postprandial gastrointestinal hyperemia is most likely chemically induced.