Modulation of endothelium-dependent hyperpolarization and relaxation to acetylcholine in rat mesenteric artery by cytochrome P450 enzyme activity

Twelve Hereford steers (average BW = 231 kg) that had previously grazed native rangeland (Range) or irrigated winter wheat pasture (Wheat) were allowed to graze locoweed-infested rangeland from April 1 to June 9, 1994 (six steers/previous grazing treatment). Relative consumption level of locoweed and other forage classes was measured as observed bites per steer. Liver biopsy and whole blood samples were obtained from each steer before and after grazing. Liver samples were analyzed for several minerals by inductively coupled plasma-atomic emission spectroscopy, and whole blood samples were analyzed for Se. Liver concentrations of Ba (P < .001), Cd (P < .001), Ca (P < .01), Cr (P < .01), Ni (P < .001), Na (P < .01), and V (P < .001) were greater and concentrations of Mn (P < .09), P (P < .01), and K (P < .07) were less in Wheat than in Range steers. Liver concentrations of Fe, Mg, S, and Zn and whole blood Se concentrations did not differ (P > .10) between the two groups. Liver concentrations of Cr (P < .04) and Mn (P < .001) were less, and Fe concentrations were greater (P < .01), in samples taken after grazing than in samples taken before grazing of locoweed-infested range. Whole blood Se concentrations decreased (P < .01) from the beginning to the end of the grazing period, but this effect was not related (P > .15) to locoweed consumption. Changes in liver concentrations of minerals were compared relative to consumption levels of all forage classes in the locoweed-infested range. Liver concentrations of Cu decreased (r2 = .45; P < .02) as the percentage of bites consumed as locoweed increased, but concentrations after grazing locoweed-infested range were still within normal ranges. Changes in liver concentrations of other minerals were not related (P > .15) to consumption of locoweed. These data indicate that previous grazing history can have significant effects on liver mineral stores and that, under our conditions, consumption of locoweed by grazing beef steers altered liver Cu concentrations. Toxic effects of locoweed consumption would likely occur before Cu deficiency would be induced by grazing locoweed-infested range; hence, supplementation of Cu would seem unlikely to alter the course of locoweed toxicosis.     

Evidence that potassium channels make a major contribution to SIN-1-evoked relaxation of rat isolated mesenteric artery

1. The NO donor 3-morpholino-sydnonimine (SIN-1; 0.01-10 microM) evoked concentration-dependent relaxation of rat isolated mesenteric arteries pre-constricted with phenylephrine (1-3 microM). The relaxation to SIN-1 was not significantly different between endothelium-intact or denuded arterial segments or segments in which basal nitric oxide (NO) synthesis was inhibited (n = 8; P > 0.05). In contrast, the membrane permeable analogue of guanosine 3':5'-cyclic monophosphate (cyclic GMP), 8-Br-cyclic GMP (0.01-1 mM), was much less effective in relaxing intact than denuded arterial segments or intact arterial segments pre-incubated with NO synthase blockers (n = 4; P < 0.01). 2. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microM; 10 min) alone, did not alter SIN-1-evoked relaxation in any tissues (n = 5; P > 0.05). However, in parallel experiments, ODQ almost completely inhibited both basal and SIN-1-stimulated production of cyclic GMP in both the presence and absence of NO synthase blockers (n = 6; P < 0.01) indicating that full relaxation to SIN-1 can be achieved in the absence of an increase in cyclic GMP. 3. Exposure of endothelium-intact arterial segments to the potassium channel blocker charybdotoxin (50 nM; 10 min), significantly inhibited SIN-1-evoked relaxation, reducing the maximum response by around 90% (n = 5; P < 0.01). In contrast, in arterial segments in which either the endothelial cell layer had been removed or basal NO synthesis inhibited, relaxation to SIN-1 was not reduced in the presence of charybdotoxin (n = 6; P > 0.05). However, in the presence of NO synthase blockers and L-arginine (300 microM) together, charybdotoxin did significantly inhibit SIN-1-evoked relaxation to a similar extent as intact tissues (maximum response induced by around 80%; n = 4; P < 0.01). 4. Pre-incubation with apamin (30 nM; 10 min) or glibenclamide (10 microM; 10 min) did not alter SIN-1-evoked relaxation of phenylephrine-induced tone in any tissues (n = 4 and n = 6, respectively; P > 0.05). However, in the presence of either ODQ and apamin, or ODQ and glibenclamide, SIN-1-evoked relaxation was significantly attenuated in intact arterial segments and segments in which NO synthesis was blocked. 5. Exposure of intact arterial segments to charybdotoxin and apamin, in the presence of NO synthase blockers, also significantly inhibited SIN-1-evoked relaxation, reducing the maximum response by around 80% (n = 4; P < 0.01). 6. Addition of superoxide dismutase (SOD; 30 u ml-1), potentiated relaxations to SIN-1 in all tissues, but did not alter the effects of charybdotoxin and ODQ and SIN-1-evoked relaxation. 7. These data show that although relaxation to the NO-donor SIN-1 is not significantly different between endothelium-intact and denuded arterial segments, the mechanisms which mediate SIN-1-evoked relaxation in the rat isolated mesenteric artery appear to be modulated by the basal release of endothelium-derived NO. In the presence of an intact endothelial cell layer, the major mechanism for SIN-1-evoked relaxation appears to be the activation of charybdotoxin-sensitive potassium channels. In contrast, when basal NO synthesis is inhibited, SIN-1 appears to cause full relaxation by both the activation of a charybdotoxin-sensitive pathway and the stimulation of soluble guanylyl cyclase.     

N-acetylcysteine enhances endothelium-dependent vasorelaxation in the isolated rat mesenteric artery

Coronary disease in cardiac transplant patients is a major factor in the limitation of long term survival. The aim of this study was to compare the results of angioscopy with those of coronary angiography performed systematically every 18 months in our center. Twenty-nine patients (31 angioscopies) were assessed 38 +/- 21 months after transplantation. The appearance observed by angioscopy were: 1) normal, 2) yellow pigmentation of the arterial surface, 3) elevated plaque < 50%, 4) elevated plaque > or = 50% stenosis. Angiography was: 1) normal, 2) iregularities of the lumen or < 50% stenosis, 3) > or = 50% stenosis. The films were viewed by two independent investigators. Angioscopy was performed on the left anterior descending artery (N = 35), the left circumflex (N = 24) and the right coronary artery (N = 9). One to three arterial segments were examined per vessel (total of 117 segments: average 3.8 segments per patient). Angioscopy was uniterpretable in 13/117 (11%) of cases. Of the 81 (78%) segments considered normal at coronary angiography, only 55 seemed normal at angioscopy (68%). Of the 23 segments considered to be abnormal at coronary angiography, all were also considered to be abnormal at angioscopy. The authors conclude that coronary angioscopy seems to be more sensitive than coronary angiography for the detection of coronary disease due to chronic rejection. Prospective studies are required to determine whether the infra-angiographic angioscopic lesions correspond to earlier stages of coronary disease of the cardiac graft.     

Glibenclamide-sensitive mechanism is involved in helodermin-produced vasodilatation in rat mesenteric artery

Helodermin-caused vascular relaxation was simultaneously measured with intracellular Ca2+ concentration ([Ca2+]i) in rat mesenteric artery. Helodermin caused concentration-dependent relaxation in the mesenteric artery preconstricted with norepinephrine (NE). Helodermin-caused relaxation was accompanied by decrease in [Ca2+]i, D-cis-Diltiazem, a Ca2+ channel blocker, also lowered the [Ca2+]i and tension increased by NE. However, helodermin relaxed the artery more efficiently than D-cis-diltiazem, suggesting that the peptide decreased myofilament Ca2+ sensitivity. The vascular relaxation and the corresponding decrease in [Ca2+]i induced by helodermin were partly, but significantly attenuated by glibenclamide. Helodermin-induced vascular responses were mimicked by vasoactive intestinal polypeptide (VIP) or forskolin. Furthermore, helodermin increased cAMP contents in the mesenteric artery. These findings show that vasodilatation induced by helodermin is attributable to lowered [Ca2+]i of arterial smooth muscle partly through the activation of glibenclamide-sensitive K+ channels, and to decrease in the myofilament Ca2+ sensitivity. The increase in the cellular cAMP content probably plays a key role in the peptide-induced vasorelaxation.     

Heat acclimation does not alter rat mesenteric artery response to norepinephrine

Previous studies have shown that heat acclimation raises the temperature threshold for heat-induced splanchnic vasoconstriction in the rat (W. Haddad and M. Horowitz. Thermal Balance in Health and Disease, Advances in Pharmacological Sciences. Basel: Birkhauser, 1994, p. 203-208; M. Shochina, W. Haddad, U. Meiri, and M. Horo-witz. J. Therm. Biol. 21: 289-295, 1996). We tested the hypothesis that heat acclimation alters splanchnic resistance artery sensitivity to norepinephrine (NE). Male Sprague-Dawley rats (n = 5) were acclimated to 35 degreesC ambient temperature for 5-8 wk. Control rats (n = 5) were maintained at 22-23 degreesC ambient temperature for 5-7 wk. Small mesenteric artery segments (2- to 3-mm length, 100- to 340-micrometer ID) were isolated, cannulated at both ends, and pressurized to 50 mmHg. Artery luminal diameter was measured in response to cumulative doses of NE (10(-9) to 10(-5) M) by using video microscopy. NE dose response was measured at 37 and 43 degreesC bath temperatures. There were no differences in constriction responses to NE between acclimated and control rat arteries at either 37 or 43 degreesC. We conclude that acclimation does not alter rat mesenteric artery sensitivity to NE.     

The actions of some cannabinoid receptor ligands in the rat isolated mesenteric artery

Premature ovarian failure (POF) is a defect of ovarian development and is characterized by primary or secondary amenorrhea, with elevated levels of serum gonadotropins, or by early menopause. The disorder has been attributed to various causes, including rearrangements of a large "critical region" in the long arm of the X chromosome. Here we report identification, in a family with POF, of a gene that is disrupted by a breakpoint. The gene is the human homologue of the Drosophila melanogaster diaphanous gene; mutated alleles of this gene affect spermatogenesis or oogenesis and lead to sterility. The protein (DIA) encoded by the human gene (DIA) is the first human member of the growing FH1/FH2 protein family. Members of this protein family affect cytokinesis and other actin-mediated morphogenetic processes that are required in early steps of development. We propose that the human DIA gene is one of the genes responsible for POF and that it affects the cell divisions that lead to ovarian follicle formation.     

A comparison of EDHF-mediated and anandamide-induced relaxations in the rat isolated mesenteric artery

1. Relaxation of the methoxamine-precontracted rat small mesenteric artery by endothelium-derived hyperpolarizing factor (EDHF) was compared with relaxation to the cannabinoid, anandamide (arachidonylethanolamide). EDHF was produced in a concentration- and endothelium-dependent fashion in the presence of NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) by either carbachol (pEC50 [negative logarithm of the EC50] = 6.19 +/- 0.01, Rmax [maximum response] = 93.2 +/- 0.4%; n = 14) or calcium ionophore A23187 (pEC50 = 6.46 +/- 0.02, Rmax = 83.6 +/- 3.6%; n = 8). Anandamide responses were independent of the presence of endothelium or L-NAME (control with endothelium: pEC50 = 6.31 +/- 0.06, Rmax = 94.7 +/- 4.6%; n = 10; with L-NAME: pEC50 = 6.33 +/- 0.04, Rmax = 93.4 +/- 6.0%; n = 4). 2. The selective cannabinoid receptor antagonist, SR 141716A (1 microM) caused rightward shifts of the concentration-response curves to both carbachol (2.5 fold) and A23187 (3.3 fold). It also antagonized anandamide relaxations in the presence or absence of endothelium giving a 2 fold shift in each case. SR 141716A (10 microM) greatly reduced the Rmax values for EDHF-mediated relaxations to carbachol (control, 93.2 +/- 0.4%; SR 141716A, 10.7 +/- 2.5%; n = 5; P < 0.001) and A23187 (control, 84.8 +/- 2.1%; SR 141716A, 3.5 +/- 2.3%; n = 6; P < 0.001) but caused a 10 fold parallel shift in the concentration-relaxation curve for anandamide without affecting Rmax. 3. Precontraction with 60 mM KCl significantly reduced (P < 0.01; n = 4 for all) relaxations to 1 microM carbachol (control 68.8 +/- 5.6% versus 17.8 +/- 7.1%), A23187 (control 71.4 +/- 6.1% versus 3.9 +/- 0.45%) and anandamide (control 71.1 +/- 7.0% versus 5.2 +/- 3.6%). Similar effects were seen in the presence of 25 mM K+. Incubation of vessels with pertussis toxin (PTX; 400 ng ml-1, 2 h) also reduced (P < 0.01; n = 4 for all) relaxations to 1 microM carbachol (control 63.5 +/- 7.5% versus 9.0 +/- 3.2%), A23187 (control 77.0 +/- 5.8% versus 16.2 +/- 7.1%) and anandamide (control 89.8 +/- 2.2% versus 17.6 +/- 8.7%). 4. Incubation of vessels with the protease inhibitor phenylmethylsulphonyl fluoride (PMSF; 200 microM) significantly potentiated (P < 0.01), to a similar extent (approximately 2 fold), relaxation to A23187 (pEC50: control, 6.45 +/- 0.04; PMSF, 6.74 +/- 0.10; n = 4) and anandamide (pEC50: control, 6.31 +/- 0.02; PMSF, 6.61 +/- 0.08; n = 8). PMSF also potentiated carbachol responses both in the presence (pEC50: control, 6.25 +/- 0.01; PMSF, 7.00 +/- 0.01; n = 4; P < 0.01) and absence (pEC50: control, 6.41 +/- 0.04; PMSF, 6.88 +/- 0.04; n = 4; P < 0.001) of L-NAME. Responses to the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) were also potentiated by PMSF (pEC50: control, 7.51 +/- 0.06; PMSF, 8.00 +/- 0.05, n = 4, P < 0.001). 5. EDHF-mediated relaxation to carbachol was significantly attenuated by the K+ channel blocker tetraethylammonium (TEA; 1 mM) (pEC50: control, 6.19 +/- 0.01; TEA, 5.61 +/- 0.01; n = 6; P < 0.01). In contrast, TEA (1 mM) had no effect on EDHF-mediated relaxation to A23187 (pEC50: control, 6.47 +/- 0.04; TEA, 6.41 +/- 0.02, n = 4) or on anandamide (pEC50: control, 6.28 +/- 0.06; TEA, 6.09 +/- 0.02; n = 5). TEA (10 mM) significantly (P < 0.01) reduced the Rmax for anandamide (control, 94.3 +/- 4.0%; 10 mM TEA, 60.7 +/- 4.4%; n = 5) but had no effect on the Rmax to carbachol or A23187. 6. BaCl2 (100 microM), considered to be selective for blockade of inward rectifier K+ channels, had no significant effect on relaxations to carbachol or A23187, but caused a small shift in the anandamide concentration-response curve (pEC50: control, 6.39 +/- 0.01; Ba2+, 6.20 +/- 0.01; n = 4; P < 0.01). BaCl2 (1 mM; which causes non-selective block of K+ channels) significantly (P < 0.01) attenuated relaxations to all three agents (pEC50 values: carbachol, 5.65 +/- 0.02; A23187, 5.84 +/- 0.04; anandamide, 5.95 +/- 0.02; n = 4 for each). 7. Apamin (1mu M), a selective blocker of small conductance, Ca2+-activated, K+ channels (SKCa), 4-aminopyridine (1mM), a blocker of delayed rectifier, voltage-dependent, K+ channels (Kv), and ciclazindol (10mu M), an inhibitor of Kv and adenosine 5'-triphosphate (ATP)-sensitive K+ channels (KATP), significantly reduced EDHF-mediated relaxations to carbachol, but had no significant effects on A23187 or anandamide responses. 8. Glibenclamide (10mu M), a KATP inhibitor and charybdotoxin (100 or 300nM), a blocker of several K+ channel subtypes, had no significant effect on relaxations to any of the agents. Iberiotoxin (50nM), an inhibitor of large conductance, Ca2+-activated, K+ channels (BKCa), had no significant effect on the relaxation responses, either alone or in combination with apamin (1muM). Also, a combination of apamin (1muM) with either glibenclamide (10muM) or 4-aminopyridine (1mM) did not inhibit relaxation to carbachol significantly more than apamin alone. Neither combination had any significant effect on relaxation to A23187 or anandamide. 9. A combination of apamin (1muM) with charybdotoxin (100nM) abolished EDHF-mediated relaxation to carbachol, but had no significant effect on that to A23187. Apamin (1muM) and charybdotoxin (300nM) together consistently inhibited the response to A23187, while apamin (1muM) and ciclazindol (10muM) together inhibited relaxations to both carbachol and A23187. None of these toxin combinations had any significant effect on relaxation to anandamide. 10. It was concluded that the differential sensitivity to K+ channel blockers of EDHF-mediated responses to carbachol and A23187 might be due to actions on endothelial generation of EDHF, as well as its actions on the vascular smooth muscle, and suggests care must be taken in choosing the means of generating EDHF when making comparative studies. Also, the relaxations to EDHF and anandamide may involve activation of cannabinoid receptors, coupled via PTX-sensitive G-proteins to activation of K+ conductances. The results support the hypothesis that EDHF is an endocannabinoid but relaxations to EDHF and anandamide show differential sensitivity to K+ channel blockers, therefore it is likely that anandamide is not identical to EDHF in the small rat mesenteric artery.     

Mechanisms of relaxation of coronary artery by hypoxia

This study was designed to clarify the dependency of hypoxic coronary vasodilation (HCD) on the endothelium and the role of the K+ channels on HCD in the rabbit coronary artery. HCD was investigated in an isolated left circumflex coronary artery precontracted with prostaglandin F2 alpha. Vascular rings were suspended for isometric tension recording in an organ chamber filled with Krebs-Henseleit (KH) solution. Hypoxia was induced by gassing the chamber with 95% N2 + 5% CO2 and was maintained for 15 approximately 25 min. Hypoxia elicited a vasodilation in the precontracted coronary artery with and without endothelium. There was no difference between the amplitude of the HCD induced by two consecutive hypoxic challenges and the effects of 20% O2 + 5% CO2 + 75% N2 and 95% O2 + 5% CO2 control K-H solution of subsequent responses to hypoxia. Inhibition of the cyclooxygenase pathway by treatment with indomethacin had no effect on HCD. Blockades of the tetraethylammonium chloride-sensitive K+ channel abolished HCD. Apamin, a blocker of the small conductance Ca(2+)-activated K+ (KCa) channel, and iberiotoxin, a blocker of the large conductance KCa channel had no effect on HCD, respectively. Glibenclamide, a blocker of the ATP-sensitive K+ (K+ATP) channel, reduced HCD. Cromakalim, an opener of the K+ATP channel, relaxed the coronary artery precontracted with prostaglandin F2 alpha. The degree of relaxation by cromakalim was similar to that by hypoxia while glibenclamide reduced both hypoxia- and cromakalim-induced vasodilatations. In conclusion, these results suggest that HCD is independent on endothelium and HCD is considered to be induced by activation of K+ATP channel.     

Duodenal trichobezoar caused by compression of the superior mesenteric artery

Trichobezoars can occur in young women who have a history of trichotillomania, trichophagia, gastric dysmotility, and psychiatric dysfunction. A 6-year-old anorexic girl presented with a fixed right-upper-quadrant abdominal mass. Exploratory celiotomy for a duodenal trichobezoar led to removal of the large foreign body, via a duodenotomy, and prompted a Ladd procedure, in which the duodenum was moved from beneath the compressing superior mesenteric artery to relieve underlying duodenal narrowing.     

Characterization of alpha1-adrenoceptor subtypes mediating contractions to phenylephrine in rat thoracic aorta, mesenteric artery and pulmonary artery

1. The subtype of alpha1-adrenoceptor mediating contractions to phenylephrine of the rat thoracic aorta, mesenteric artery and pulmonary artery were investigated by use of antagonists which show selectivity between the cloned alpha1-adrenoceptor subtypes in binding studies. 2. Cumulative concentration-contraction curves for phenylephrine were competitively antagonized in the rat thoracic aorta by prazosin (pA2 9.9), WB4101 (pA2 9.6), 5-methylurapidil (pA2 8.1), benoxathian (pA2 9.2) and indoramin (pA2 7.4). These compounds were also competitive antagonists in the mesenteric and pulmonary arteries (except for 5-methylurapidil in the pulmonary artery), (prazosin pA2 9.9 and 9.7; WB4101 pA2 9.8 and 9.6; 5-methylurapidil pA2 7.9 and pK(B) estimate 8.0; benoxathian pA2 8.8 and 9.3; indoramin pA2 7.2 and 7.5, respectively). 3. RS 17053 was not a competitive antagonist in any blood vessel as Schild plot slopes were greater than unity. The pK(B) estimates for RS 17053 were 7.1 in aorta, 7.0 in the mesenteric artery and 7.7 in the pulmonary artery. 4. The alpha1D-subtype selective antagonist BMY 7378 appeared to be non-competitive with shallow Schild plot slopes. The data were better fitted with two lines in all tissues, with Schild plot slopes that were no longer different from unity, except in the pulmonary artery. The higher affinity site for BMY 7378 in the aorta had a pA2 of 9.0, while it was 8.8 and 8.9 in the mesenteric and pulmonary arteries, respectively. 5. MDL73005EF acted in a non-competitive manner in all three blood vessels, with shallow Schild plot slopes. The pK(B) estimates for MDL73005EF were 8.4 in aorta, 7.5 in the mesenteric artery and 8.0 in the pulmonary artery. 6. In all three blood vessels the functionally determined antagonist affinity estimates correlated best with published pKi values for their displacement of [3H]-prazosin binding on membranes expressing cloned alpha1d-adrenoceptors compared with alpha1a- or alpha1b-adrenoceptors. The antagonist affinity estimates in the aorta, mesenteric and pulmonary arteries correlated highly with their previously published pA2 values in rat aorta (alpha1D) and less well with those for alpha1A- and alpha1B-adrenoceptors mediating contraction of the rat epididymal vas deferens and rat spleen, respectively. 7. The results of this study suggest that the contraction to phenylephrine of the rat thoracic aorta, mesenteric artery and pulmonary artery are mediated in part via the alpha1D-subtype of adrenoceptor. The data for both BMY 7378 and MDL73005EF in all three blood vessels are consistent with receptor heterogeneity. However, the identity of the second site is unclear.     

Prejunctional effects of cromakalim, nicorandil and pinacidil on noradrenergic transmission in rat isolated mesenteric artery

Quil A used with Boophilus microplus gut membrane antigen (GM) had a significant effect on antibody levels induced in sheep (P < 0.05) since GM alone did not induce a significant level of antibodies. Injection of a vaccine containing GM and Quil A, either subcutaneously or intramuscularly, induced similar levels of antibodies in sheep. However, Quil A injected subcutaneously induced acute inflammatory reaction. The amount of Quil A for use with GM was determined to be 1000 micrograms/ml. Immunostimulating complexes (ISCOMs) incorporating detergent-solubilized membrane midgut antigens (TX-GM) failed to induce an immune response in cattle without the addition of Quil A. The addition of Quil A to the ISCOMs containing TX-GM did not stimulate antibody responses greater than those stimulated by TX-GM plus Quil A, and protection in vaccinated cattle was 86% and 74%, respectively.     

Superior mesenteric artery blood flow in celiac disease

Measurements of the hemodynamic parameters of the superior mesenteric artery were performed in 18 patients with celiac disease. Ten were studied at the time of diagnosis, when a small bowel biopsy showed a flat mucosa. The remaining eight patients were studied after complete clinical and histological recovery induced by a gluten-free diet. Doppler ultrasound flowmetry was used to measure blood flow in physiological and fasting conditions and after a mixed liquid test meal (Ensure-Plus). The results were compared with those of healthy subjects (N = 7). Mean basal flow was 50% higher in untreated celiac disease patients than in healthy controls and patients with chronic pancreatitis (P = NS). Postprandial mesenteric blood flow was significantly increased (P < 0.002) and delayed in time (P < 0.005) in celiac disease as compared to controls. Successful treatment reduced the mesenteric blood flow in celiac disease to normal values. Our study demonstrates that pathophysiological changes in the small bowel mucosa during the active clinical phase of celiac disease induce an abnormal splanchnic circulation.     

Sources of Ca2+ in relation to generation of acetylcholine-induced endothelium-dependent hyperpolarization in rat mesenteric artery

1. The aim of the present study was to identify the sources of Ca2+ contributing to acetylcholine (ACh)-induced release of endothelium-derived hyperpolarizing factor (EDHF) from endothelial cells of rat mesenteric artery and to assess the pathway involved. The changes in membrane potentials of smooth muscles by ACh measured with the microelectrode technique were evaluated as a marker for EDHF release. 2. ACh elicited membrane hyperpolarization of smooth muscle cells in an endothelium-dependent manner. The hyperpolarizing response was not affected by treatment with 10 microM indomethacin, 300 microM NG-nitro-L-arginine or 10 microM oxyhaemoglobin, thereby indicating that the hyperpolarization is not mediated by prostanoids or nitric oxide but is presumably by EDHF. 3. In the presence of extracellular Ca2+, 1 microM ACh generated a hyperpolarization composed of the transient and sustained components. By contrast, in Ca(2+)-free medium, ACh produced only transient hyperpolarization. 4. Pretreatment with 100 nM thapsigargin and 3 microM cyclopiazonic acid, endoplasmic reticulum Ca(2+)-ATPase inhibitors, completely abolished ACh-induced hyperpolarization. Pretreatment with 20 mM caffeine also markedly attenuated ACh-induced hyperpolarization. However, the overall pattern and peak amplitude of hyperpolarization were unaffected by pretreatment with 1 microM ryanodine. 5. In the presence of 5 mM Ni2+ or 3 mM Mn2+, the hyperpolarizing response to ACh was transient, and the sustained component of hyperpolarization was not observed. On the other hand, 1 microM nifedipine had no effect on ACh-induced hyperpolarization. 6. ACh-induced hyperpolarization was nearly completely eliminated by 500 nM U-73122 or 200 microM 2-nitro-4-carboxyphenyl-N, N-diphenylcarbamate, inhibitors of phospholipase C, but was unchanged by 500 nM U-73343, an inactive form of U-73122. Pretreatment with 20 nM staurosporine, an inhibitor of protein kinase C, did not modify ACh-induced hyperpolarization. 7. These results indicate that the ACh-induced release of EDHF from endothelial cells of rat mesenteric artery is possibly initiated by Ca2+ release from inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ pool as a consequence of stimulation of phospholipid hydrolysis due to phospholipase C activation, and maintained by Ca2+ influx via a Ni(2+)- and Mn(2+)-sensitive pathway distinct from L-type Ca2+ channels. The Ca(2+)-influx mechanism seems to be activated following IP3-induced depletion of the pool.     

Albumin kinetics in superior mesenteric artery shock in rats

1. After 1-hour-tourniquet of the arteria mesenterical superior of the rat the result is a loss of intravasal fluid into the small intestine. After 2-hour-tourniquet the loss of fluid into the samll intestine can be higher than the volume of plasma circulating at the start of the experiment. During therapy with plasma substitute on base of gelatine (Haemaccel) the volume of content of the small intestine increases further. 2. After 1-hour-tourniquet the content of intravasal albumin is diminished by 26%, after 2-hour-tourniquet by 46%. Under therapy with a plasma substitute the loss of intravasal albumin increases further. 3. After 1-hour-tourniquet a transient accumulation of albumin was found in the wall of the samll intestine which was reduced after 2-hour-tourniquet. 4. The intravasal albumin is excreted in the small and the large intestine. After 1-hour-tourniquet 46% of excreted albumin was found in the small intestine after 2-hour-tourniquet 61%. It can be demonstrated, that under replacement with plasma substitute the result is mainly an "albumin dilution effect". The wall of the small intestine becomes permeable to high-molecular weight substances with an average molecular weight below 60.000. An effective therapy with the plasma substitute of the AMS-shock should, therefore, contain carrier substances with a molecular weight higher than 60.000.     

CT angiography of superior mesenteric artery syndrome

OBJECTIVE: Our purpose was to describe the use of CT angiography and three-dimensional (3D) reconstruction in the diagnosis of superior mesenteric artery syndrome in three patients. CONCLUSION: CT angiography combined with 3D reconstructions is a noninvasive technique that may have a complementary diagnostic role similar to that of angiography in patients with a classic clinical presentation suggestive of superior mesenteric artery syndrome. CT angiography combined with 3D reconstructions should be considered in patients who might otherwise require angiography.     

Mechanism of endothelium-dependent relaxation induced by thrombin in the pig coronary artery

The present study describes the characterization of the binding properties and autoradiographic distribution of a new nonpeptide antagonist of neurotensin receptors, [3H]SR 142948A (2-[[5-(2,6-dimethoxyphenyl)-1-(4-(N-(3-dimethylaminopropyl)-N-methyl carbamoyl)-2-isopropylphenyl)-1H-pyrazole-3-carbonyl]-amino]-ad amantane-2-carboxylic acid, hydrochloride), in the rat brain. The binding of [3H]SR 142948A in brain membrane homogenates was specific, time-dependent, reversible and saturable. [3H]SR 142948A bound to an apparently homogeneous population of sites, with a Kd of 3.5 nM and a Bmax value of 508 fmol/mg of protein, which was 80% higher than that observed in saturation experiments with [3H]neurotensin. [3H]SR 142948A binding was inhibited by SR 142948A, the related nonpeptide receptor antagonist, SR 48692 (2-[[1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)-1H-pyrazole -3-carbonyl]amino]-adamantane-2-carboxylic acid) and neurotensin. Saturation and competition studies in the presence or absence of the histamine H1 receptor antagonist, levocabastine, revealed that [3H]SR 142948A bound with similar affinities to both the levocabastine-insensitive neurotensin NT1 receptors (20% of the total binding population) and the recently cloned levocabastine-sensitive neurotensin NT2 receptors (80% of the receptors) (Kd = 6.8 and 4.8 nM, respectively). The regional distribution of [3H]SR 142948A binding in the rat brain closely matched the distribution of [125I]neurotensin binding. In conclusion, these findings indicate that [3H]SR 142948A is a new potent antagonist radioligand which recognizes with high affinity both neurotensin NT1 and NT2 receptors and represents thus an excellent tool to study neurotensin receptors in the rat brain.     

Superior mesenteric artery aneurysm in Beh?et's disease

Beh?et's disease is a multisystem disorder characterized by recurrent orogenital ulcerations and uveitis. Vascular involvement can include both arteries and veins, with a preponderance of venous lesions. Aneurysms of splanchnic arteries due to Beh?et's disease have been rarely reported. We present an unusual case of superior mesenteric artery aneurysm due to Beh?et's disease diagnosed by ultrasonography and angiography.     

Effects of glucagon on superior mesenteric artery and femoral artery haemodynamics in humans

OBJECTIVE: It remains unclear whether glucagon is a localized splanchnic arterial vasodilator in humans. This study examined this issue by assessing the haemodynamic effect of exogenous glucagon on splanchnic and extrasplanchnic arteries. METHODS: After an overnight fast, flow velocity of superior mesenteric artery and femoral artery was recorded by means of echo-Doppler in 10 controls and 10 patients with cirrhosis. Mean arterial pressure, heart rate and plasma glucagon level were also determined. These measurements were repeated after intramuscular injection of glucagon (1 mg) at 15 min and 30 min. RESULTS: Patients with cirrhosis had much higher glucagon levels than controls (P < 0.01). Plasma glucagon level rose following glucagon administration in controls (P < 0.01) and patients with cirrhosis (P < 0.01). Glucagon administration had no effect on mean arterial pressure, heart rate and femoral artery velocity in controls and patients with cirrhosis. In contrast, superior mesenteric artery velocity significantly increased after glucagon administration in both groups (P < 0.01, P < 0.01), although the effect was less pronounced in patients with cirrhosis than in controls (P < 0.05). CONCLUSION: These data suggest that glucagon might be a localized splanchnic arterial vasodilator. Thus, glucagon may be one of the factors contributing to the pathogenesis of the splanchnic hyperdynamic circulation seen in patients with cirrhosis.