Increase In Intestinal Blood Flow Research Articles

Electrical stimulation of the vagus nerve improves intestinal blood flow after trauma and hemorrhagic shock

BackgroundGut damage after trauma/hemorrhagic shock contributes to multiple organ dysfunction syndrome. Electrical vagal nerve stimulation is known to prevent gut damage in animal models of trauma/hemorrhagic shock by altering the gut inflammatory response; however, the effect of vagal nerve stimulation on intestinal blood flow, which is an essential function of the vagus nerve, is unknown. This study aimed to determine whether vagal nerve stimulation influences the abdominal vagus nerve activity, intestinal blood flow, gut injury, and the levels of autonomic neuropeptides. MethodsMale Sprague Dawley rats were anesthetized, and the cervical and abdominal vagus nerves were exposed. One pair of bipolar electrodes was attached to the cervical vagus nerve to stimulate it; another pair of bipolar electrodes were attached to the abdominal vagus nerve to measure action potentials. The rats underwent trauma/hemorrhagic shock (with maintenance of mean arterial pressure of 25 mmHg for 30 min) without fluid resuscitation and received cervical vagal nerve stimulation post-injury. A separate cohort of animals were subjected to transection of the abdominal vagus nerve (vagotomy) just before the start of cervical vagal nerve stimulation. Intestinal blood flow was measured by laser Doppler flowmetry. Gut injury and noradrenaline level in the portal venous plasma were also assessed. ResultsVagal nerve stimulation evoked action potentials in the abdominal vagus nerve and caused a 2-fold increase in intestinal blood flow compared to the shock phase (P < .05). Abdominal vagotomy eliminated the effect of vagal nerve stimulation on intestinal blood flow (P < .05). Vagal nerve stimulation protected against trauma/hemorrhagic shock -induced gut injury (P < .05), and circulating noradrenaline levels were decreased after vagal nerve stimulation (P < .05). ConclusionCervical vagal nerve stimulation evoked abdominal vagal nerve activity and relieved the trauma/hemorrhagic shock–induced impairment in intestinal blood flow by modulating the vasoconstriction effect of noradrenaline, which provides new insight into the protective effect of vagal nerve stimulation.

Developmental Changes in Mesenteric Artery Reactivity in Fetal and Perinatal Chicks

Background and aims: The fetal intestine presents a low-flow, high-resistance vascular bed. Birth is accompanied by a dramatic increase in intestinal blood flow. The vascular changes accompanying this transition have been partly characterized. Here, we aimed to investigate the developmental changes in chick mesenteric artery (MA) reactivity during the fetal and perinatal period. Methods: Rings of the distal segment of the cranial MA from 15-d (F15) and 19-d (F19) chicken fetuses (total incubation: 21d) as well as non-fed 0-3-h-old (NH3h) and first-fed 1-d-old (NH1d) newly hatched (NH) chicks were mounted in a wire myograph. Results: F15 MA rings responded to KCl-evoked depolarization and to norepinephrine (NE), thromboxane A2 (U46619), endothelin (ET)-1, acetylcholine (ACh), sodium nitroprusside (SNP), and forskolin indicating the presence of electro- and pharmaco-mechanical coupling as well as cGMP- and cAMP-mediated relaxation. The contractile efficacy of KCl underwent a linear increase (F15< F19< NH3h< NH1d). The efficacy of NE and U46619 increased in ovo but not ex ovo (F15< F19=NH3h=NH1d) and the efficacy of ET-1 peaked at F19. The relaxations elicited by ACh, SNP, and forskolin did not undergo dramatic developmental changes. Hypoxia induced contraction in MA rings. F15 MAs did not respond to hypoxia and the hypoxic responsiveness did not change ex-ovo (F15=0< F19< NH3h=NH1d). Conclusions: The ability of chick MAs to constrict in response to pharmacological and physical stimuli increases during the fetal period but no dramatic changes are induced by hatching or the first feeding. Maturation of vasodilator mechanisms precedes that of vasoconstrictor mechanisms.

Factors that influence mesenteric artery blood flow velocity in newborn preterm infants

To identify demographic and clinical variables that relate to the postnatal increase in intestinal blood flow velocity in preterm infants. Fasting or preprandial peak systolic velocity (PSV) and time-averaged mean velocity (TAMV) in the superior mesenteric artery were measured once each day for the first 5 days of life. We investigated the relationship between blood flow velocity and the following variables: birth weight, gestational age, feeding volumes, number of days to reach full feeding volumes, type of feeding given, continuous positive airway pressure (CPAP) administration and hyperalimentation (HAL) administration. Twenty-five infants with a mean birth weight of 1740 g and mean gestational age of 31.8 weeks were studied. There were significant increases in PSV (P < 0.001) and TAMV (P = 0.005) from postnatal day 1 to 5. The postnatal increase in TAMV and PSV was attenuated in infants administered CPAP or HAL for > or =3 days; the results remained significant after controlling for birth weight and gestational age. There was a significant correlation (P < 0.02) between volume of enteral feedings given on 2 of 5 days for TAMV, and on 1 of 5 days for PSV. These data support previous findings of significant increases in intestinal blood flow in preterm infants during the first week of life, and of inconsistent effects of enteral feeding volumes on fasting or preprandial intestinal blood flow. The reasons for, and the clinical implications of, attenuated increases in postnatal intestinal blood flow in infants on CPAP or HAL require further investigation.

The herbal medicine Dai-kenchu-to and one of its active components [6]-shogaol increase intestinal blood flow in rats

The present study investigated the effects of the herbal medicine Dai-kenchu-to (DKCT) and its 4 individual ingredients on intestinal blood flow (IBF) in rats by laser Doppler flowmetry. Intraduodenal administration of DKCT (30, 100 and 300 mg/kg) increased IBF in a dose-dependent manner, whereas the mean arterial blood pressure was not affected. One of the ingredients in DKCT is dried ginger rhizome (150 mg/kg), whose main component is [6]-shogaol (2 mg/kg), both of which showed similar effects to those shown by DKCT, while the other ingredients in DKCT only slightly increased IBF or had no effect. The calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP (8–37), completely abolished the hyperemia induced by DKCT, dried ginger rhizome and [6]-shogaol. However, the vasoactive intestinal polypeptide (VIP) receptor antagonist, [4-Cl-DPhe6, Leu17]-VIP, and atropine were less inhibitory than CGRP (8–37), and the substance P (SP) receptor antagonist, spantide, had no effect. The present study demonstrated that DKCT and one of its active components, [6]-shogaol, produced an increase in IBF which was mainly mediated by CGRP and suggests that DKCT may be useful in the treatment of intestinal ischemia-related diseases.

Propionate-induced relaxation in rat mesenteric arteries: a role for endothelium-derived hyperpolarising factor.

Short chain fatty acids, including propionate, are generated in the caecum and large intestine, and when absorbed may elicit localised increases in intestinal blood flow. We sought to assess the mechanism by which propionate caused vasorelaxation. Propionate-mediated relaxation of noradrenaline-preconstricted rat mesenteric small arteries (RMSAs, i.d. 200-300 microm) was studied using small vessel myography. Propionate (1-30 mM) produced a concentration-dependent relaxation. Relaxation induced by 10 mM propionate (the approximate EC50) was almost abolished by endothelial denudation, although a marked relaxation to a very high concentration of propionate (50 mM) persisted in the absence of the endothelium. In endothelium-intact RMSAs, relaxation to 10 mM propionate was almost abolished by elevating [K+]o to 25 mM, but was unaffected by 100 microM N(omega)-nitro-L-arginine methyl ester (L-NAME) (68 +/- 4 vs. 66 +/- 3% in controls, n = 35), or by 1 microM indomethacin (60 +/- 4 vs. 61 +/- 7 % in controls, n = 15). In the presence of L-NAME, relaxation to 10 mM propionate was significantly and markedly (i.e. > 50 %) inhibited by 50 microM Ba2+ and by the combination of 100 nM charybdotoxin and 100 nM apamin. A similar effect on propionate-mediated relaxation was also exerted by 100 microM ouabain, and by the combination of 50 microM barium with ouabain. Relaxation was also significantly and markedly inhibited by pre-treatment of RMSAs with 100 nM thapsigargin or 10 microM cyclopiazonic acid (CPA). The results demonstrate that 10 mM propionate relaxes RMSAs via endothelium-derived hyperpolarising factor (EDHF). The observation that relaxation by propionate is inhibited by thapsigargin and CPA suggests that this action of propionate involves the release of endothelial cell Ca2+ stores.

Circulatory responses to a meal in patients with a newly transplanted heart.

It is well established that consumption of a meal releases a gradually developing and quite marked increase in blood flow to the gastrointestinal organs and a similar and simultaneous increase in cardiac output (CO). It is not known through which mechanism the pumping of the heart adjusts so accurately to the gastrointestinal flow increase. We have approached this problem by serving a standardized, mixed meal to five patients with recently transplanted and thus denervated hearts and to five sex- and age-matched controls. Pre- and postprandial levels of CO and blood flow in the superior mesenteric artery (SMA) were recorded with Doppler ultrasound technique. The patients with transplanted hearts had significantly higher preprandial levels of heart rate (HR) and CO than the controls. With a timing similar to that seen in the controls did all five patients develop considerable and synchronous postprandial increases in superior mesenteric arterial flow and in CO. Increases in superior mesenteric arterial flow were significantly greater than the controls. Also, COs, high even before meals were given, increased further and to the same relative extent as in the control persons. The marked postprandial increase in CO, probably secondary to the increase in intestinal blood flow, could hardly come about through any sort of nervous reflex to the recently transplanted and denervated hearts. It appears more likely that a humoral connection of some sort exists between the two circulatory events.

ATP-MgCL2Reduces Intestinal Permeability during Mesenteric Ischemia

ATP-MgCl2has been demonstrated to have beneficial attributes in numerous models of organ ischemia. In this study we examined whether ATP-MgCl2could decrease permeability in ischemic segments of rat ileum. Ileal segments (nonischemic and ischemic) from the same rat were cannulated and perfused, and the plasma to lumen clearance of51Cr-EDTA was measured. Ischemia increased permeability from a baseline value of 0.59 ± 0.14 (mean ± SEM in ml/min/g dry wt of intestine) to 1.10 ± 0.14 at 90 min (n= 12), significantly higher than that of the nonischemic segments (0.55 ± 0.07) at 90 min (P< 0.05). This was associated with a significant reduction in blood flow from 0.84 ± 0.08 (n= 4) (mean ± SEM ml/min/g wet wt of intestine) to 0.16 ± 0.06 (n= 4) (P< 0.05) as measured by labeled microspheres. Rats receiving ATP-MgCl2(100 μmol) (n= 8) pretreatment showed no increase in clearance over 90 min (baseline 0.69 ± 0.07; 90 min 0.70 ± 0.07) and no significant difference in blood flow from untreated ischemic segments (0.21 ± 0.9) (n= 4). Tissue ATP levels determined enzymatically were significantly reduced by 5 min postischemia to 4.19 ± 0.35 (n= 7) (P< 0.05) from a control value of 6.77 ± 0.77 μmol/g dry wt (n= 14). ATP levels remained depressed at 30 min (3.45 ± 0.35) and 90 min (3.38 ± 0.26). ATP-MgCl2treatment did not significantly alter these tissue ATP levels. These data indicate that ATP-MgCl2prevents the increase of51Cr-EDTA permeability during ischemia without alterations in tissue ATP levels or increases in intestinal blood flow.

Preservation of postprandial intestinal hyperemic response after small bowl transplantation

Postprandial intestinal hyperemia (PIH) is a normal physiological phenomenon and is thought to accommodate the increased intestinal metabolic demand during food digestion. Lack of such a response could lead to malabsorption. The purpose of this study was to determine whether transplanted intestine retains the ability to mediate PIH. Nineteen rats with syngeneic orthotopic small bowel transplantation (SBT) and 13 normal controls were further divided into two subgroups to receive gastric gavage of either 2 mL of Ensure Plus (EP) high-calorie liquid nutrition or 2 mL of normal saline. Intestinal blood flow was determined before, and 20 and 45 minutes after the gavage, employing a colored microsphere technique. The results showed that basal blood flow to the transplanted intestine (56.7 ± 26.7 mL/min/100 g) was similar to that of normal intestine (64.2 ± 35.8 mL/min/100 g; P > .1). EP feeding elicited a marked increase in intestinal blood flow (PIH phenomenon) in both normal and SBT animals. The magnitudes of flow increase were similar for the two groups (249 ± 99% versus 241 ± 76% of baseline 45 minutes after EP feeding in the normal and transplanted intestine, respectively; P > .1). The results indicate that hyperemic response to feeding is normal in syngeneic orthotopic SBT.

Peptidergic nerves mediate post-nerve stimulation hyperemia in rat gut.

Cessation of perivascular nerve stimulation (NS) elicits a transient increase in intestinal blood flow above the prestimulatory value. This enhancement of blood flow constitutes the phenomenon of post-nerve stimulation hyperemia (PSH). We investigated the involvement of peptidergic sensory nerves in intestinal PSH. In anesthetized rats the velocity of blood flowing through the anterior mesenteric artery (VBF) was measured with a pulsed Doppler velocimeter. PSH was induced by 4 min of postganglionic electrical NS (5 Hz). PSH was abolished by distal periarterial application of tetrodotoxin and intra-arterial lidocaine, which suggests a peripheral sensory nervous mechanism for PSH. The increase in conductance at peak PSH was blocked by pretreatment with the selective, primary afferent neurotoxin capsaicin administered as 1) subcutaneous injection in neonatal life, 2) topical application to periarterial nerves, or 3) injection into the jejunal lumen. In rats pretreated with reserpine, NS evoked a hyperemic response, which was blocked by capsaicin. Treatment with adenosine deaminase inhibited PSH considerably less than capsaicin, suggesting a lesser role for adenosine in PSH. Our findings support the hypothesis that postganglionic NS activates both adrenergic and peptidergic nerves and that the latter release vasodilator peptides in the gut during PSH.

Blood flow in experimental short bowel syndrome

Mechanisms of intestinal adaptation after major loss of small bowel have been studied extensively but little attention has been paid to related changes in blood flow. In 1972, Touloukian and Spencer were the first to study intestinal blood flow after 50% midintestinal resection in rats [16]. In the present study an 80% midintestinal resection was performed in rats (n = 54). Blood flows to the jejunal and ileal remnants, the anastomosis, and the cecum and colon were measured with the radioactive microsphere method on days 1, 2, 3, 5, and 28 after surgery. Results were compared with blood flow estimates after jejunal or ileal tranection (n = 48) and with normal controls (n = 9). The results showed that the operative stress of intestinal transection is followed by a brief increase in intestinal blood flow. After 80% small-bowel resection, intestinal blood flow remains more significantly elevated for at least 3 days. Blood flow to the ileal remnant remains elevated for at least 4 weeks after surgery. The mechanisms responsible for the increase in blood flow remain to be defined.

The effects of mefenamic acid on postprandial intestinal carbohydrate metabolism

The effects of mefenamic acid on the food-induced changes in intestinal carbohydrate metabolism were determined in an attempt to elucidate the mechanism(s) by which inhibition of prostaglandin synthesis enhances the postprandial increases in intestinal blood flow and oxygen consumption. The data show that when the luminal perfusate was was changed from saline to a nutrient/bile solution, there was an increase in carbohydrate utilization, which was offset by absorption of glucose from the lumen. Intravenous administration of mefenamic acid significantly increased both carbohydrate absorption and metabolism when food was placed in the lumen. Changes in carbohydrate absorption and metabolism have been shown to play an important role in determining the magnitude of glucose induced changes in intestinal blood flow and oxygen consumption. Therefore, it is possible that the ability of mefenamic acid to enhance significantly the food-induced increases in blood flow and oxygen consumption may be due in part to its effects on intestinal carbohydrate absorption and utilization.

Regulation of intestinal blood flow with increased intraluminal pressure

To better characterize the mechanisms which regulate intestinal blood flow (IBF), we studied the effects of gradual and rapid increases in intraluminal pressure (LP) in anesthetized canines. Polarographic measurements of hydrogen washout allowed repeated assessment of IBF (ml/min · g) in control (CL) and distended (DL) autoperfused small intestinal loops. In group I ( n = 7) graded increases in LP (mm Hg) were produced by saline inflation. In group II ( n = 4), IBF was measured before and after intraarterial aminophylline (adenosine blockade); LP was then rapidly raised to 24 mm Hg. IBF was unchanged by time (CL 0.64 ± 0.24) or gradual distension (DL 0.65 ± 0.28 at mean maximal LP = 26). Aminophylline did not change IBF at LP = 0. Rapid distension after adenosine blockade was accompanied by immediate increases in IBF (0.96 ± 0.41, P < 0.05) and decreased resistance (50 ± 25% control). IBF is maintained despite gradual increases in luminal pressure. Blockade of adenosine, an intestinal vasodilator, does not inhibit this response; hyperemia associated with rapid distension is not impaired. We conclude that autoregulation of IBF during distension is not accomplished by an adenosine mediated metabolic mechanism.

Contribution of hyperosmolality to glucose-induced intestinal hyperemia

To test the hypothesis that changes in tissue osmolality participate in glucose-induced absorptive hyperemia, the mucosa of the rat jejunum was suffused with isotonic or hypertonic glucose solutions. Blood flow was calculated from the product of a constant, arteriolar diameter, and red blood cell velocity, which were measured in the submucosal microcirculation. Isotonic glucose solutions (293 +/- 2 mosmol/kg) were prepared by diluting 5, 10, or 20 ml of 5% glucose, which is isotonic with plasma, to 100 ml with Ringer-bicarbonate buffer to concentrations of 250, 500, and 1,000 mg/100 ml. Glucose was added directly to Ringer-bicarbonate buffer to increase osmolality. The osmolalities of the 250, 500, and 1,000 mg/100 ml hypertonic solutions were 305 +/- 3,319 +/- 3, and 353 +/- 1 mosmol/kg, respectively. Glucose caused a concentration-related increase in estimated submucosal arteriolar blood flow that averaged 18-21% (n = 14), 24-27% (n = 14), and 34-45% (n = 14) at 250, 500, and 1,000 mg/100 ml glucose, respectively. There was no effect of solution osmolality on either the time course or the magnitude of the hyperemia at a given glucose concentration. Whereas the magnitude of the glucose-induced hyperemia averaged less than 50%, the application of 10(-2) M adenosine caused a fivefold increase in calculated blood flow (492 +/- 67%, n = 24). Thus, glucose caused relatively small increases in intestinal blood flow. If changes in luminal osmolality caused changes in intestinal tissue osmolality, then it is unlikely that hyperosmolality participates in the functional hyperemia associated with glucose absorption.

Reduced vascular sensitivity to norepinephrine in portal-hypertensive rats.

The development of portal hypertension following chronic portal vein stenosis is accompanied by a significant increase in intestinal blood flow. The present study was designed to determine whether intestinal vascular sensitivity to norepinephrine (NE) is also affected by chronic portal vein stenosis. Using a blood-perfused, in situ rat small intestine preparation, we found that, when compared with control animals, a significantly greater molar concentration of NE was required to achieve the same proportional increase in intestinal vascular resistance in portal-hypertensive animals. The mean ED50 value (+/-SE) for the portal-hypertensive group (704.3 +/- 186.1 nM) was significantly greater (P less than 0.05) than the mean ED50 value for the control group (271.4 + 48.1 nM). This finding implies that sympathetic maintenance of intestinal vascular tone may be impaired following chronic portal vein stenosis, possibly accounting for part of the intestinal hyperemia associated with portal hypertension.

Arachidonic acid and postprandial intestinal hyperemia

The effects of prostaglandin synthesis on food-induced increases in intestinal blood flow and O2 uptake were examined in the jejunum of anesthetized dogs. Intravenous (40 micrograms X kg-1 X min-1) or intra-arterial (0.8-1.6 microgram X min-1) infusions and luminal placement (6.5 X 10(-4) M or 200 micrograms/ml) of arachidonic acid (AA) significantly attenuated the food-induced jejunal hyperemia. Furthermore, luminal placement of AA significantly attenuated the food-induced increase in jejunal O2 uptake. Changes in blood flow and O2 uptake were significantly correlated both before and after arachidonic acid administration. Although intravenous infusion of AA decreased blood flow, intra-arterial infusion and luminal placement of AA did not significantly alter resting blood flow under free-flow conditions. In another series of experiments, intravenous infusions of AA under constant-flow conditions produced a biphasic response: vascular resistance rose when local blood AA concentration was raised to the range between 1 and 6 micrograms/ml blood and fell when the concentration was raised between 8 and 12 micrograms/ml blood. This study indicates that prostaglandin synthesis has a marked effect on both resting intestinal blood flow and postprandial intestinal hyperemia. The attenuation of the hyperemia may be due to its attenuation of the food-induced increase in intestinal oxidative metabolism.

Possible involvement of capsaicin-sensitive sensory nerves in the regulation of intestinal blood flow in the dog.

The effect of capsaicin injected into the superior mesenteric artery has been studied on the intestinal blood flow in dogs. Capsaicin evoked a marked dose-dependent increase in mesenterial blood flow in the dose range of 0.1-7 micrograms/kg. The intestinal vasodilatatory effect of capsaicin could invariably be demonstrated after pretreatment with adrenoceptor and dopamine receptor antagonists, as well as with the ganglion blocking agent hexamethonium. Pretreatment with atropine significantly reduced, but did not abolish the increase in intestinal blood flow elicited by capsaicin. Concomitant administration of somatostatin significantly inhibited both the atropine-sensitive and the atropine-resistant components of the effect of capsaicin injected into the superior mesenteric artery. Our results indirectly support the assumption that the intestinal vasodilatatory effect of capsaicin may be mediated by substance P release from capsaicin-sensitive paravascular nerve fibres associated with the blood vessels of the gastrointestinal tract. It is suggested that sensory substance P-containing nerve fibres may be involved in the regulation of the vascular reactions of the gut.

Intestinal Blood Flow and Oxygen Consumption

In this study, we examined the effects of both pharmacologically and mechanically induced increases in intestinal blood flow on intestinal oxygen consumption. Intraarterial infusions of prostacyclin (1-20 ng X kg-1 X min-1) significantly increased both blood flow and oxygen consumption under free flow conditions. However, the increase in oxygen consumption appears to be due to the corresponding increase in blood flow rather than a direct effect of prostacyclin on intestinal metabolism. This conclusion is supported by the finding that a mechanically induced increase in intestinal blood flow (60%) can also produce an increase in intestinal oxygen consumption (24%). These findings support the hypothesis that intestinal oxygen consumption is flow-dependent over a wide range of blood flows.

The role of 5-hydroxytryptamine in the feline response to intravenous infusion of live E. coli.

A standardized septic shock was induced in cats by intravenous infusion of a live E. coli bacteria strain. The bacterial infusion induced a rapid haemodynamic response characterized mainly by a pulmonary arterial hypertension and a late phase characterized by systemic hypotension and hypodynamic circulation. Systemic arterial, pulmonary arterial, portal venous, left atrial pressures, max inspiratory-expiratory pressure difference in the trachea, aortic and intestinal blood flows were monitored. Arterial blood samples were taken for recording the number of circulating platelets and white blood cells and for determining the acid-base balance. The effect of pretreatment with ketanserin, a specific 5-hydroxytryptamine2 (5-HT2)-receptor blocker on these haemodynamic reactions was studied. In short term experiments on non-bacteriaemic control cats, ketanserin prevented the pulmonary hypertension induced by intravenous 5-HT infusions but not the increase in intestinal blood flow. Ketanserin induced a reduction of total peripheral (including intestinal) vascular resistance to blood flow but had no effect on aortic blood flow. After infusion of bacteria, ketanserin pretreated cats were more hypotensive due to a relative peripheral dilatation of the resistance vessels. Ketanserin pretreatment had no effect on the pulmonary vascular reactions, the tracheal pressure difference or the number of circulating platelets or white blood cells. Thus, except for a more pronounced hypotension early after bacterial infusion, ketanserin pretreatment did not influence the haemodynamic response. It is concluded that 5-HT is not of significant importance in the pathogenesis of the haemodynamic reactions following experimental bacteraemia.

Neurotensin-induced increase in intestinal blood flow in the anesthetized rat.

Cardiac output (CO) and blood flow to major organs were investigated in pentobarbital-anesthetized rats using 85Sr and 141Ce labelled microspheres (MS) of 15 microns diameter injected into the left ventricle. Changes in organ blood flow and CO were measured after intraventricular dextran (3.4 mumol/kg/min) and intravenous neurotensin (NT) at two different rates, 2.5 nmol/kg/min and 0.125 nmol/kg/min. Dextran, known to give anaphylactoid response in rats, reduced the mean arterial pressure (MAP) from 118 +/- 17 to 55 +/- 8 mmHg (p less than 0.001) concomitant with a 56% decline in CO and significant decreases in blood flow to most organs. At 2.5 nmol/kg/min, NT caused a pattern of changes in MAP, CO and organ blood flow similar to that obtained with dextran, and thus consistent with an indirect response via mast cell stimulation. NT injected at 0.125 nmol/kg/min resulted in a significant increase (30%) in blood flow to the small intestine (p less than 0.01) without changes in MAP or CO. Vascular resistance decreased by 30% in the small intestine (p less than 0.01) and by 20% in the large intestine (p less than 0.05). The results show that circulating NT, at concentrations below those eliciting hypotension, enhances intestinal blood flow without significant changes in other organs.

Effects of Adenosine and Its Derivatives on the Canine Intestinal Vasculature

The effects of adenosine and two of its structural analogs on small intestinal blood flow, flow distribution, oxygen extraction, and uptake were studied in anesthetized dogs. Adenosine induced dose-dependent increases in intestinal blood flow and oxygen consumption but decreased oxygen extraction. These effects were significantly attenuated by theophylline, an adenosine antagonist. Propranolol did not influence the responses of the intestinal circulation to adenosine suggesting that beta-adrenergic receptors are not involved in the action of adenosine. 2-Chloroadenosine, one of the most potent adenosine analogs, produced changes very similar to adenosine but was about six times more potent on a molar basis. Effects of 2-chloroadenosine were attenuated by a 10-fold smaller dose of theophylline. Adenosine-9 beta-D-arabinofuranoside, another analog, was ineffective in the mesenteric circulation. Characteristic activity of both analogs and the antagonism of the effects of adenosine and 2-chloroadenosine by theophylline suggest the presence of adenosine-sensitive binding sites in precapillary resistance vessels of the intestinal circulation. The presence of adenosine receptors in intestinal vascular smooth muscle is further supported by our in vitro results in which all three agents induce patterns of response similar to those noted under in vivo conditions. However, concentrations necessary to obtain relaxation of isolated muscle strips were much greater than those sufficient to produce mesenteric vasodilation in vivo. It was also noted that strips obtained from branches of the superior mesenteric artery were more reactive to adenosine and its analogs than were strips prepared from the main trunk of the vessel.