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Isolated celiac artery vasculitis is an uncommon disease rarely reported in the Western literature. In this case report, we describe a 52-year-old Chinese male presenting with abdominal pain who was diagnosed with nonspecific celiac artery vasculitis and was successfully treated with a short course of oral corticosteroids., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives To describe our clinical experiences and recommend a management strategy for spontaneous isolated dissection of a visceral artery. Methods A retrospective study of patients from December 2005 to December 2015 was performed. Thirty-two patients had spontaneous isolated dissection of a visceral artery. Clinical features, computed tomography findings, the treatment method, and follow-up results were evaluated. Results There were 28 men and 4 women (mean age, 54 years). Dissection locations were the celiac artery in 10, superior mesenteric artery in 17, and celiac artery and superior mesenteric artery in 5 patients. Celiac artery stenosis existed with spontaneous isolated dissection of a visceral artery at a high rate. After diagnosis, the blood pressure of all patients was immediately controlled to a lower level. Three patients with arterial rupture and one patient with bowel infarction underwent operations for complications. Overall, the treatment of dissection involved drug therapy alone. The last follow-up computed tomography results of the true lumen residual ratio and the length of the dissected artery improved compared to the values on admission; the maximum diameter of the dissected artery did not enlarge. Eleven patients almost completely improved. No patients had any adverse event. Conclusions Most patients with spontaneous isolated dissection of a visceral artery can be first treated conservatively for dissection with strict blood pressure control and surveillance.

Objective: Isolated dissection of the mesenteric vessels is rare but increasingly recognized. This study aimed to evaluate patient characteristics, primary treatment, and subsequent outcomes of mesenteric dissection using multi-institutional data., Methods: All patients at participant hospitals between January 2003 and December 2015 with dissection of the celiac artery (or its branches) or dissection of the superior mesenteric artery (SMA) were included. Patients with an aortic dissection were excluded. Demographic, treatment, and follow-up data were collected. The primary outcomes included late vessel thrombosis (LVT) and aneurysmal degeneration (AD)., Results: Twelve institutions identified 227 patients (220 with complete treatment records) with a mean age of 55 ± 12.5 years. Median time to last follow up was 15 months (interquartile range, 3.8-32). Most patients were men (82% vs 18% women) and symptomatic at presentation (162 vs 65 asymptomatic). Isolated SMA dissection was more common than celiac artery dissection (n = 158 and 81, respectively). Concomitant dissection of both arteries was rare (n = 12). The mean dissection length was significantly longer in symptomatic patients than in asymptomatic patients in both the celiac artery (27 vs 18 mm; P = .01) and the SMA (64 vs 40 mm; P < .001). Primary treatment was medical in 146 patients with oral anticoagulation or antiplatelet therapy (n = 76 and 70, respectively), whereas 56 patients were observed. LVT occurred in six patients, and 16 patients developed AD (3% and 8%, respectively). For symptomatic patients without evidence of ischemia (n = 134), there was no difference in occurrence of LVT with medical therapy compared with observation alone (9% vs 0%; P = .35). No asymptomatic patient (n = 64) had an episode of LVT at 5 years. AD rates did not differ among symptomatic patients without ischemia treated with medical therapy or observed (9% vs 5%; P = .95). Surgical or endovascular intervention was performed in 18 patients (3 ischemia, 13 pain, 1 AD, 1 asymptomatic). Excluding the patients treated for ischemia, there was no difference in LVT with surgical intervention vs medical management (one vs five; P = .57)., Conclusions: Asymptomatic patients with isolated mesenteric artery dissection may be observed and followed up with intermittent imaging. Symptomatic patients tend to have longer dissections than asymptomatic patients. Symptomatic isolated mesenteric artery dissection without evidence of ischemia does not require anticoagulation and may be treated with antiplatelet therapy or observation alone., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

This confirmatory work is aimed to test that the hypothesis that the gastrin releasing peptide (GRP) receptor - the BB2 receptor - is necessary for reduction of meal size (MS) and prolongation of the intermeal interval (IMI) by the small and the large forms of GRP in the rat, GRP-10 and GRP-29, and to confirm the sites of action regulating such responses - the vascular bed of the celiac artery (CA, supplying stomach and upper duodenum). To pursue these aims we measured first MS and IMI length in response to GRP-10 and GRP-29 (0, 0.5nmol/kg) infused in the CA (n=8 rats) and the cranial mesenteric artery (CMA, supplying the small and part of the large intestine, n=8 rats) in near spontaneously free feeding rats pretreated with the BB2 receptor antagonist BW2258U89 (0.1mg/kg) in the same arteries prior to the onset of the dark cycle. We found that GRP-29, but not GRP-10, infused by the CA reduced MS and prolonged the IMI by decreasing meal latency and meal duration and the BB2 receptor antagonist BW2258U89 infused in the same artery attenuated these responses. These results suggest that the BB2 receptor is necessary for reduction of MS and prolongation of the IMI by exogenous GRP-29, and the vascular bed of the CA, stomach and upper duodenum, contains sites of action regulating these feeding responses., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Two separate experiments were performed to localize the gastrointestinal sites of action regulating meal size (MS), intermeal interval (IMI) length and satiety ratio (SR, IMI/MS) by cholecystokinin (CCK) 8 and 33. Experiment 1: CCK-8 (0, 0.05, 0.15, 0.25nmol/kg) was infused in the celiac artery (CA, supplies stomach and upper duodenum) or the cranial mesenteric artery (CMA, supplies small and part of the large intestine) prior to the onset of the dark cycle in free feeding, male Sprague Dawley rats and MS (normal rat chow), IMI and SR were recorded. Experiment 2: CCK-33 (0, 0.05, 0.15, 0.25nmol/kg) were infused in the CA or the CMA, under the same experimental conditions above, and MS, IMI and SR were recorded. Experiment 1 found that CCK-8 reduces MS, prolongs the IMI and increases the SR at sites supplied by both arteries. Experiment 2 found that CCK-33 reduces MS and increases the SR at sites supplied by the CMA. We conclude that in male rats the feeding behaviors evoked by CCK-33, but not CCK-8, are regulated at specific gastrointestinal sites of action., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Three experiments were done to better assess the gastrointestinal (GI) site(s) of action of GLP-1 on food intake in rats. First, near-spontaneous nocturnal chow meal size (MS), intermeal intervals (IMI) length and satiety ratios (SR = MS/IMI) were measured after infusion of saline, 0.025 or 0.5 nmol/kg GLP-1 into the celiac artery (CA, supplying the stomach and upper duodenum), cranial mesenteric artery (CMA, supplying small and all of the large intestine except the rectum), femoral artery (FA, control) or portal vein (PV, control). Second, infusion of 0.5 nmol/kg GLP-1 was tested after pretreatment with the GLP-1 receptor (GLP-1R) antagonist exendin-4(3-39) via the same routes. Third, the regional distribution of GLP-1R in the rat GI tract was determined using rtPCR. CA, CMA and FA GLP-1 reduced first MS relative to saline, with the CMA route more effective than the others. Only CMA GLP-1 prolonged the IMI. None of the infusions affected second MS or later eating. CA and CMA GLP-1 increased the SR, with the CMA route more effective than the CA route. CMA exendin-4 (3-39) infusion reduced the effect of CMA GLP-1. Finally GLP-1R expression was found throughout the GI tract. The results suggest that exogenous GLP-1 acts in multiple GI sites to reduce feeding under our conditions and that GLP-1R in the area supplied by the CMA, i.e., the small and part of the large intestine, plays the leading role., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Despite the advancement in the postoperative care of neonates with congenital heart disease (CHD), there is little information on preoperative management of systemic and regional hemodynamics, which may be related to outcomes. We aimed to determine the preoperative effect of milrinone, a phosphodiesterase III inhibitor, on cardiac output and splanchnic and cerebral perfusion in neonates with CHD. Neonates with CHD requiring cardiac surgery were enrolled in a prospective, single-blinded study once a clinical decision of starting milrinone (0.75 μg/kg per minute intravenously) using institutional criteria was made. Demographic and clinical variables and outcomes were recorded. Combined cardiac output and measures of splanchnic (superior mesenteric and celiac arteries) and cerebral (anterior and middle cerebral arteries) perfusion were determined by Doppler studies at 0, 6, 24, and 48 h after milrinone infusion. Investigators were unaware of intervention time points and patients in analyzing blood flow measurements. Seventeen term (39.2 ± 1.3 weeks) neonates were included with hypoplastic left-sided heart syndrome (78.5%) as the most common diagnosis. Combined cardiac output increased by 28% within 48 h (613 ± 154 vs. 479 ± 147 mL/kg per minute at baseline, P < 0.05). Superior mesenteric artery mean velocity increased at 6 h and throughout 48 h of milrinone infusion (P < 0.05). Peak and mean velocities at cerebral arteries increased with milrinone infusion (P < 0.05~0.08), and the corresponding changes at celiac artery were modest. There were no significant changes in splanchnic and cerebral resistive and pulsatility indices during milrinone infusion. Milrinone increases cardiac output with concurrent effects on splanchnic and cerebral blood flows during the short-term preoperative use in neonates with CHD.

Gastric leptin elicits its cardiovascular and splanchnic sympathoinhibitory responses via a vagal afferent mechanism, however the latter are blunted/abolished in animals fed a medium high fat diet (MHFD). In a diet-induced obesity model we sought to determine whether the renal sympathetic nerve discharge (RSND) and regional vasodilator responses to gastric leptin are also affected by diet and/or obesity. The diet induced obesity model was used in 2 separate studies. After 13 weeks on a MHFD the animals were classified as either obesity prone (OP) or obesity resistant (OR) depending on their weight gain. Control animals were fed a low fat diet for an equivalent period. Arterial pressure (AP) and heart rate (HR) were monitored in isoflurane-anaesthetised, artificially ventilated animals and RSND or regional vascular responses to leptin (15 μg/kg) administered close to the coeliac artery were evaluated. OP rats had higher baseline AP compared to control/OR rats (P<0.05). Close arterial leptin inhibited RSND in control animals but this response was abolished in OR and OP animals (P<0.01 for both). Leptin administration increased renal vascular conductance in control animals but this response was significantly attenuated only in OP animals (P<0.05). The vasodilator response in the superior mesenteric artery was not significantly different in any of the groups (P>0.05). Together these results suggest that, while the renal sympathoinhibitory responses to gastric leptin are affected by diet, the vasodilator responses to leptin in the renal vascular bed are only affected in OP animals. These changes may impact on cardiovascular homeostatic mechanisms in obesity., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to evaluate the potential for intravenous vasopressin to reduce the risk of nontarget gastrointestinal embolization during transcatheter liver-directed cancer therapies in a porcine model., Materials and Methods: An angiographic catheter was used to select the celiac or common hepatic artery under fluoroscopic guidance in six anesthetized pigs. After angiography of the hepatic and splanchnic territories was performed, technetium-99m macroaggregated albumin ((99m)Tc-MAA) was injected through the catheter. Serial arteriograms were obtained before, every 5 minutes during, and after peripheral intravenous vasopressin infusion at 0.4 U/min for a minimum of 20 minutes. After 10 minutes of infusion, indium-111 ((111)In)-MAA was injected through the arterial catheter. Quantitative comparisons of liver and gastrointestinal activity using dual-isotope single-photon emission computed tomography (SPECT)/CT imaging were performed., Results: Catheter angiography demonstrated reduced blood flow to the splanchnic vasculature while maintaining blood flow through the hepatic arteries during vasopressin infusion. Angiographic findings correlated with the relative distribution of (99m)Tc-MAA (before the vasopressin infusion) and (111)In-MAA (after the vasopressin infusion) on SPECT/CT. The increased ratio of liver to gastrointestinal tract activity during the vasopressin infusion was statistically significant (6.2:11.4, respectively; P = .018)., Conclusions: Intravenous vasopressin reduces arterial blood flow to the splanchnic vasculature while preserving hepatic arterial blood flow in a healthy porcine model. Intraprocedural vasopressin administration has the potential to benefit liver-directed cancer therapies by enhancing tumor targeting as well as preventing the unintended delivery of bland embolic, chemoembolic, or radioembolic agents into the gastrointestinal vascular territories., (Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.)

Takayasu's arteritis (TA) is an inflammatory vasculitis of aorta and its branches, its low incidence limited our recognition to this entity. We sometimes can confuse this disease with polyarteritis nodosa and other vasculitis when no conventional "big artery" involved in TA cases. Here we report a 26-year-old man with Takayasu's arteritis who presented with a provisional intracranial granulomatosis first and then saccular aneurysms between celiac trunk and arteria hepatica communis and many other proteus manifestations, which is seldom described before.

Objectives: To measure the effects of fenoldopam mesylate infusion on splanchnic blood flow in patients undergoing myocardial revascularization with cardiopulmonary bypass., Design: An experimental observational study., Setting: A single-institution community hospital., Participants: Eighteen patients undergoing on-pump coronary artery bypass graft surgery., Interventions: Fenoldopam mesylate infusion (0.1 μg/kg/min)., Measurements and Main Results: Blood flow through the celiac artery, superior mesenteric artery, portal vein and hepatic artery were assessed by means of Doppler measurements. The main hemodynamic variables were measured using echocardiography. The infusion of fenoldopam significantly increased the blood flow through both celiac and superior mesenteric arteries by decreasing vascular resistance. The percentage of cardiac output directed to these 2 vessels increased significantly; the increase through the superior mesenteric artery was greater compared with the celiac artery. Portal vein and hepatic artery blood flow also consistently increased. No significant variations were observed with respect to hemodynamic variables., Conclusions: The infusion of fenoldopam increased the flow through the celiac artery and superior mesenteric artery; the effect was higher for the latter. These changes did not affect the hemodynamic variables., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The presence and vasoactive effects of native calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A (NKA) were studied on isolated small branches of the coeliac artery from Atlantic cod, Gadus morhua, using immunohistochemistry and myograph recordings, respectively. Immunohistochemistry revealed nerve fibers containing CGRP- and SP/NKA-like material running along the wall of the arteries. CGRP induced vasorelaxation of precontracted arteries with a pD(2) value of 8.54 +/- 0.17. Relaxation to CGRP (10(-8) M) was unaffected by L-NAME (3 x 10(-4) M) and indomethacin (10(-6) M) suggesting no involvement of nitric oxide or prostaglandins in the CGRP-induced relaxation. SP and NKA (from 10(-10) to 3 x 10(-7) M) contracted the unstimulated arteries at concentrations from 10(-8) M and above in 42% and 33%, respectively, of the vessels. It is concluded that the innervation of the cod celiac artery includes nerves expressing CGRP-like and tachykinin-like material, and that a vasodilatory response to CGRP is highly conserved amongst vertebrates while the response to tachykinins is more variable.

Background: A single high loading dose of 25 mg/kg caffeine has been shown to be effective for the prevention of apnoea, but may result in considerable reductions in blood flow velocity (BFV) in cerebral and intestinal arteries., Objective: To assess the effects of two loading doses of 12.5 mg/kg caffeine given four hours apart on BFV in cerebral and intestinal arteries, left ventricular output (LVO), and plasma caffeine concentrations in preterm infants., Design: Sixteen preterm neonates of <34 weeks gestation were investigated one hour after the first oral dose and one, two, and 20 hours after the second dose by Doppler sonography., Results: The mean (SD) plasma caffeine concentrations were 31 (7) and 29 (7) mg/l at two and 20 hours respectively after the second dose. One hour after the first dose, none of the circulatory variables had changed significantly. One hour after the second caffeine dose, mean BFV in the internal carotid artery and anterior cerebral artery showed significant reductions of 17% and 19% (p = 0.01 and p = 0.003 respectively). BFV in the coeliac artery and superior mesenteric artery, LVO, PCO2, and respiratory rate had not changed significantly. Total vascular resistance, calculated as the ratio of mean blood pressure to LVO, had increased significantly one and two hours after the second dose (p = 0.049 and p = 0.023 respectively)., Conclusion: A divided high loading dose of 25 mg/kg caffeine given four hours apart had decreased BFV in cerebral arteries after the second dose, whereas BFV in intestinal arteries and LVO were not affected.

1. Rho-kinase (ROK) stimulation represents a key step in the maintenance of agonist-induced contraction, an effect counteracted by nitric oxide (NO) released from the endothelium. The aim of the present study was to characterize the involvement of ROK in smooth muscle contraction of the rat coeliac artery using functional and expression studies. 2. Rings of rat coeliac artery were mounted in 5 mL myographs containing warmed and oxygenated Krebs' solution. Rings were connected to isometric transducers and data were recorded in a PowerLab system (ADInstruments, Colorado Springs, CO, USA). After a 60 min equilibration period, preparations were precontracted with phenylephrine (1 micromol/L). Endothelial integrity was assessed by treating the vessels with acetylcholine (1 micromol/L). Expression of ROKalpha, ROKbeta and RhoA was analysed using western blot, whereas Rho guanine nucleotide exchange factors (RhoGEF) were measured at the mRNA level. 3. The addition of Y-27632 (0.01-30 micromol/L) caused sustained relaxation of rings contracted with phenylephrine (PE; 1 micromol/L), with intact or denuded endothelium (pEC50 = 6.38 +/- 0.03 and 5.65 +/- 0.02, respectively). NG-Nitro-L-arginine methyl ester (100 micromol/L) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 micromol/L), but not indomethacin (10 micromol/L), caused marked rightward shifts of the concentration-response curves to Y-27632. The contractile response to KCl (80 mmol/L) was significantly reduced by Y-27632, with a maximal inhibition of 57 +/- 6%. Nifedipine (0.1-100 nmol/L) fully blocked KCl-evoked contractions, but only marginally affected those in response to PE (27 +/- 2% maximal inhibition). At 1 micromol/L, Y-27632 also significantly enhanced relaxations to sodium nitroprusside (SNP; 0.0001-1 micromol/L). 4. At 1 micromol/L, SNP (but not 1 micromol/L Y-27632) significantly elevated the cGMP content above basal levels. Coincubation with SNP and Y-27632 increased cGMP levels, but the results were not significantly different from those in the presence of SNP alone. 5. Western blot analysis revealed the protein expression of RhoA, ROKalpha and ROKbeta. The PDZ-RhoGEF, p115RhoGEF and leukaemia-associated RhoGEF (LARG) mRNA expression in coeliac artery was visualized by electrophoresis on agarose gels. 6. The results clearly demonstrate a role for the RhoA/ROK signalling pathway in the regulation of rat coeliac artery smooth muscle contraction. The findings of the present study suggest that endogenous nitric oxide-induced relaxation is mediated, in part, by inhibition of RhoA/ROK signalling in this tissue.

A case of a 63-year-old man with isolated dissection of the superior mesenteric artery (SMA), demonstrated by enhanced computed tomography (CT) and abdominal angiography, was admitted to our hospital. The severity of this disease varies from mild to severe; the severe cases require surgery. But the mild cases, like the one presented here, only need conservative therapy. This case demonstrated the usefulness of anticoagulation therapy and the indications for surgical and radiological intervention.

Neuropeptide Y (NPY) has prominent cardiovascular effects in mammals and sharks, but no such effect has previously been demonstrated in any teleost fish. In the Atlantic cod, we found that cod NPY (10(-10)-10(-6) M) relaxed celiac arteries precontracted with epinephrine, and weak contractions were elicited in intestinal ring preparations. A few NPY-immunoreactive nerve fibers were present along small gut arteries. The results suggest that cod NPY produces vasorelaxation both by a direct action on smooth muscle and by release of prostaglandins, but with no involvement of nitric oxide, leukotrienes, or endothelium-derived relaxing factors. An additional indirect effect involving another neurotransmitter may occur. Cod NPY (10(-7) M) and human NPY (10(-7) M) had identical effects on the vessels. Small differences only in the effects of porcine [Leu(31),Pro(34)]NPY, NPY-(13-36), and cod NPY suggest the presence of a Y(1) subfamily receptor, similar to the zebrafish Ya receptor. A physiological role for NPY in teleost vasculature is concluded, but surprisingly the effect, a vasodilation, is opposite to that in mammals and is mediated by prostaglandins.

Objective: In adults, a single dose of 250 mg of caffeine may decrease cerebral blood flow by 30%. In preterm infants, caffeine is commonly used for the treatment and prophylaxis of apnea. The purpose of this investigation was to assess effects of caffeine on circulatory parameters in preterm infants., Methods: We studied 16 preterm neonates with a mean gestational age (mean +/- standard deviation) of 31 +/- 1.2 weeks (range: 29-33 weeks), birth weight of 1400 +/- 380 g (range: 625-2060 g), and postnatal age of 24 to 72 hours before and 1 and 2 hours after an oral loading dose of 25 mg/kg pure caffeine. We investigated left ventricular output (LVO), cerebral blood flow velocity (BFV) of the internal carotid artery (ICA) and the anterior cerebral artery, and intestinal BFV of the celiac artery and superior mesenteric artery by Doppler sonography., Results: Mean BFV in the ICA decreased significantly 1 (17%) and 2 hours (22%) after caffeine administration. Mean BFV in the anterior cerebral artery showed a reduction of 14% after 2 hours. The mean BFV in the superior mesenteric artery decreased significantly 1 and 2 hours after caffeine administration (30%). Mean BFV in the celiac artery showed a significant reduction of 14% 1 hour after caffeine. No changes were observed in LVO, blood pressure, and heart rate., Conclusion: Oral administration of a high loading dose of caffeine results in marked reduction of cerebral and intestinal BFV, without changing LVO, blood pressure, and heart rate.

The effects of [Arg(0),Trp(5),Leu(8)]-BK (cod [Arg(0)]BK) on vascular preparations from branches of the cod celiac artery and on longitudinal smooth muscle preparations from the cod intestine were investigated. Cod [Arg(0)]BK (3 x 10(-8) M) caused a relaxation of the celiac artery precontracted with adrenaline. The relaxation was abolished by the cyclooxygenase inhibitor indomethacin, suggesting that the effect is mediated through the release of prostaglandins, but there was no evidence for the involvement of leukotrienes or nitric oxide in the response. In the intestinal preparations, cod [Arg(0)]BK produced concentration-dependent contractions (pD(2) = 8.28 +/- 0.16). Experiments with N-terminally and C-terminally truncated analogs and with alanine-substituted analogs of cod [Arg(0)]BK demonstrate that the central amino acid Gly(4) and the C-terminal amino acids Leu(8) and Arg(9) are the most important in determining the conformation of the peptide that interacts with the receptor. The results indicate that the ligand binding properties of the cod BK receptor are considerably different from the receptor present in trout tissues and may resemble those of the mammalian B(2) receptor more closely.

Objective: To investigate the effects of Xuezhikang (XZhK) on the neointimal proliferation and C-myc gene expression after angioplasty in rabbits., Methods: Angioplasty for atherosclerotic stenosis of celiac arteries was performed in 30 male white rabbits after being fed with cholesterol-supplemented diet for 8 weeks, which were then randomized to control group, high-cholesterol group and XZhK group. After 4 weeks, the local vessels were collected for morphological observation. C-myc mRNA level was measured with RT-PCR and C-myc protein with immunohistochemical analysis., Results: Morphological observation showed that the neointimal area in the XZhK group were less than the control group (P < 0.05), and that in control group were less than that in the high-cholesterol group (P < 0.05). The levels of C-myc mRNA measured with RT-PCR and the percentage of C-myc protein positive cell by immunohistochemical analysis were lower in the XZhK group than in the control and high-cholesterol group (P < 0.05), The levels in the latter two groups showed no difference (P > 0.05)., Conclusion: XZhK can inhibit the neointimal proliferation and the expression of C-myc gene after angioplasty in rabbits.

Peptidergic mechanisms influencing the resistance of the gastrointestinal vascular bed of the estuarine crocodile, Crocodylus porosus, were investigated. The gut was perfused in situ via the mesenteric and the celiac arteries, and the effects of different neuropeptides were tested using bolus injections. Effects on vascular resistance were recorded as changes in inflow pressures. Peptides found in sensory neurons [substance P, neurokinin A, and calcitonin gene-related peptide (CGRP)] all caused significant relaxation of the celiac vascular bed, as did vasoactive intestinal polypeptide (VIP), another well-known vasodilator. Except for VIP, the peptides also induced transitory gut contractions. Somatostatin and neuropeptide Y (NPY), which coexist in adrenergic neurons of the C. porosus, induced vasoconstriction in the celiac vascular bed without affecting the gut motility. Galanin caused vasoconstriction and occasionally activated the gut wall. To elucidate direct effects on individual vessels, the different peptides were tested on isolated ring preparations of the mesenteric and celiac arteries. Only CGRP and VIP relaxed the epinephrine-precontracted celiac artery, whereas the effects on the mesenteric artery were variable. Somatostatin and NPY did not affect the resting tonus of these vessels, but somatostatin potentiated the epinephrine-induced contraction of the celiac artery. Immunohistochemistry revealed the existence and localization of the above-mentioned peptides in nerve fibers innervating vessels of different sizes in the gut region. These data support the hypothesis of an important role for neuropeptides in the control of the vascular bed of the gastrointestinal tract in C. porosus.

The effect of NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine methyl ester (L-NAME) on acetylcholine (ACh) induced relaxation of rat intrapulmonary artery and celiac artery ring segments was studied in vitro with and without meclofenamate pretreatment. L-NMMA, and to a lesser extent L-NAME, raised baseline tone more in pulmonary than celiac arteries. Pretreatment of pulmonary and celiac artery rings with meclofenamate did not alter this contractile effect. Pulmonary artery and celiac artery ring segments were precontracted with phenylephrine, and cumulative concentration-relaxation curves to ACh were obtained before and after incubation of the rings with L-NAME or L-NMMA. L-NAME inhibited the ACh-induced relaxation of pulmonary arterial rings at 10000 fold lower concentrations than those needed to only partly inhibit the ACh-induced relaxation of celiac artery rings. L-NMMA (10-300 microM) inhibited the ACh-induced relaxation of pulmonary arterial rings in a concentration-dependent manner, whereas L-NMMA (300 microM) only partially inhibited the ACh-induced relaxation of celiac artery rings. The inhibition of ACh-induced relaxation by L-NAME and to a lesser extent by L-NMMA was more when pulmonary and celiac artery rings were pretreated with meclofenamate (1.0 microM). These results suggest that in the pulmonary artery nitric oxide plays a greater role in the modulation of baseline vascular tone and ACh-induced relaxation than in the celiac artery. In addition, cyclooxygenase products do not contribute to the direct contractile responses to L-NAME and L-NMMA in both the pulmonary and celiac artery rings but do modulate the ACh-induced relaxation of these vessels.

Small arteries (internal diameter 376 +/- 69 microns) from the proximal intestine region of the rainbow trout were mounted in a myograph apparatus where changes in isometric tension could be recorded. VIP (vasoactive intestinal polypeptide) caused a concentration-dependent relaxation (10(-9)-3 x 10(-7) M) of vessels precontracted with the alpha-adrenoceptor agonist phenylephrine (10(-5) M). The nitric oxide synthase inhibitor L-NAME (10(-4) M) did not affect the VIP-relaxation, neither did the lipoxygenase inhibitor esculetin (10(-5) M). However, the cyclooxygenase inhibitor indomethacin (10(-6) M) shifted the concentration-response curve significantly to the right. The VIP-relaxation was still present after mechanical removal of the endothelium. Sodium nitroprusside (10(-9)-10(-6) M) caused a concentration-dependent relaxation of the precontracted vessel, indicating the presence of soluble guanylate cyclase in the vascular smooth muscle cells. VIP-immunoreactivity was found in varicose nerve fibers in these vessels, but nitric oxide synthase-immunoreactivity could not be demonstrated. These results suggest that in rainbow trout, as in mammals, VIP is an endogenous vasodilating neuropeptide. No endothelium-dependent mechanism seems to be involved, neither is production of nitric oxide. Instead the relaxation is mediated, at least in part, via prostaglandin synthesis.

Vasoconstriction caused by iodinated contrast media (CM) has been considered specific for the renal artery only. We examined the vascular effect of CM in rabbit carotid, aorta, renal, iliac, mesenteric and celiac arteries and found that other arteries also respond with a contraction to CM. Isolated arterial rings were exposed to diatrizoate (high osmolar CM), iohexol (low osmolar CM) or glucose solution, and the isometric contraction response was expressed as percentage of an initial KCl control contraction. Diatrizoate evoked contractions of 82% (carotid), 63% (aorta), 30% (renal), 24% (iliac), 28% (mesenteric) and 18% (celiac), respectively. Iohexol caused contractions of 31% (carotid), 24% (aorta), 15% (renal) and 14% (iliac), whereas the mesenteric and celiac arteries were relaxed by iohexol. A high osmolar glucose solution elicited contractions of 78%, 77%, 11%, 27%, 3% and 5%, respectively, in the arteries. CM have contraction potency in arterial vasculature other than the renal artery.

Blood flow in the coeliac trunk was measured before and after oral application of ISDN (isosorbitol dinitrate) 10 or 20 mg. Clinical prognostic value of this test was evaluated. Investigation were carried out with a duplex-Doppler pulsatory wave. The quantitative hemodynamic method with estimation of PI and RI was applied to exclude the effect of angle and the vessel diameter. 44 healthy volunteers were examined. The ultrasonograph ACUSON 128 was used with the linear and sectorial head 3.5 MHz enabling measurement of the pulsatory wave (Doppler). All persons were divided into 4 groups: according to sex, the age, the dose of nitrate and the groups given placebo. Application of the ISDN led to increase values PI and RI. Application of placebo had no influence on the blood flow.

We have investigated the modifications of cytosolic [Ca2+] and the activity of Ca2+ channels in freshly dispersed arterial myocytes to test whether lowering O2 tension (PO2) directly influences Ca2+ homeostasis in these cells. Unclamped cells loaded with fura-2 AM exhibit oscillations of cytosolic Ca2+ whose frequency depends on extracellular Ca2+ influx. Switching from a PO2 of 150 to 20 mmHg leads to a reversible attenuation of the Ca2+ oscillations. In voltage-clamped cells, hypoxia reversibly reduces the influx of Ca2+ through voltage-dependent channels, which can account for the inhibition of the Ca2+ oscillations. Low PO2 selectively inhibits L-type Ca2+ channel activity, whereas the current mediated by T-type channels is unaltered by hypoxia. The effect of low PO2 on the L-type channels is markedly voltage dependent, being more apparent with moderate depolarizations. These findings demonstrate the existence of O2-sensitive, voltage-dependent, Ca2+ channels in vascular smooth muscle that may critically contribute to the local regulation of circulation.

The aims of this study were to elucidate the vasoconstrictor mechanism that mediates the changes in celiac and mesenteric vascular resistances during vasoconstriction and hypertension induced by ganglionic blockade and to explore the preferential mechanism that contributes to the elevation of arterial pressure in conscious spontaneously hypertensive rats (SHR). In conscious SHR and normotensive control rats, blood flow and arterial pressure were measured with an implanted electromagnetic flow probe and an indwelling arterial catheter. Peripheral vascular resistance was calculated as arterial pressure divided by regional flow. Celiac contribution to the hypertension in SHR was below average for the entire body and was smaller than that from the superior mesenteric bed. The increase of mesenteric resistance with arterial pressure elevation after ganglionic blockade suggests that mesenteric blood flow is regulated by a stretch-dependent myogenic mechanism, whereas celiac blood flow is regulated preferentially by the sympathetic neural mechanism. It is speculated that the flow superregulation in the mesenteric bed in SHR is due to the enhanced myogenic response and contributes to the early stage of hypertension.

The aim of this study was the formulation of a minimal lumped model of the aortic impedance as seen in the abdominal aorta just downstream of the origin of renal arteries. At this location simultaneous measurements of pressure and flow were taken in four anesthetized and open-chest dogs (weight, 30.9 +/- 5.8 kg) under basal, vasodilated (sodium nitroprusside) and vasoconstricted (methoxamine) conditions. Using these measurements we identified and compared three lumped models, A, B, and C, with decreasing complexity from A to C. The frequency response of these models was given the general form of peripheral resistance, Rp, multiplied by the ratio between (a) two zeros and two poles (model A); (b) two zeros and one pole (model B); and (c) one zero and one pole (model C). Rp was calculated as the ratio of mean pressure to mean flow. The other model parameters (time constants, damping factors, and natural frequencies) were estimated by minimizing the sum of squared differences between experimental and model generated pulsatile flows. After parameter estimation, the F-test was applied to compare the goodness of data fit obtained from the three models. Results of this test and the analysis of parameter estimation errors indicated that model B was preferable with respect to models A and C. The analysis of general model performance was followed by a consideration of alternative specific model structures that are physically realizable. With the aid of a determined model structure we evaluated the overall compliance of terminal aortic circulation under a variety of vascular states induced by injection of vasoactive agents.

1. The importance of adenylate cyclase-mediated vascular relaxation in the macro and microcirculation was assessed in rabbit aortic and coeliac artery bioassay rings in vitro and skin microvessels in vivo. 2. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38), the beta-agonist, isoprenaline, and the prostaglandins, PGE1 and PGE2, were compared with the activity of nitroprusside, which acts by stimulating guanylate cyclase. 3. In aortic tissue the relative relaxant potencies were (-log M EC50, 100% = response to nitroprusside 10(-6) M): nitroprusside 7.0, PACAP38 6.8, isoprenaline 6.3; PGE1 and PGE2 were weak constrictors. In coeliac artery rings relative potencies were (-log M EC50, 100% = response to nitroprusside 10(-5) M): PACAP38 6.6, PGE1 6.6, nitroprusside 6.5, PGE2 4.9, and isoprenaline 4.3. 4. Comparative potencies when injected into anaesthetized rabbit skin in vivo were (-log mol/site required to increase blood red cell flux by 75%): PACAP38 13.0, PGE2 10.7, isoprenaline 9.7, PGE1 9.1, nitroprusside < 7. 5. Nitroprusside, the most effective relaxant tested in the aorta, was 10(7) fold less potent than PACAP in its effect on skin blood flow. PGE1 and PGE2 were constrictors of the aorta, of intermediate effect in the coeliac artery, but potent vasodilators of the microcirculation. 6. In this model, the importance of adenylate cyclase-mediated vascular relaxation increases with decreasing vessel size.

We postulated that the redistribution of organ blood flow that occurs in hyperdynamic sepsis is secondary to organ-specific alterations in vascular reactivity. Chronically instrumented rats were randomized to cecal ligation and perforation (CLP) (n = 12) or to a control procedure (n = 11). Cardiac output increased from 107 +/- 23 ml/min at baseline to 152 +/- 32 ml/min at 24 h after CLP (p = 0.037 versus control values). Mean blood pressure did not change in either group. Small arterial ring segment (100- to 200-microns effective lumen radius) from the pulmonary, renal, celiac, and femora arteries were obtained for determination of in vitro responsiveness. Maximal contractile responses to three receptor-operated contractile agonists were significantly depressed in the pulmonary (p = 0.001) and the celiac (p = 0.001) arteries from CLP versus control rats. The renal artery showed a trend toward decreased responsiveness (p = 0.049), but not difference was seen in the femoral artery (p = 0.172). EC50 values were unchanged. A similar, but less marked, pattern was observed for KCI-induced contractions in that depressed responses were noted in the pulmonary (p = 0.045) and celiac (p = 0.064) arteries. Vasodilator responses to acetylcholine were normal in all vessels. Nitroprusside relaxant responses were enhanced in the pulmonary artery (p = 0.022), but they were normal in the other vessels. We conclude that hyperdynamic, normotensive sepsis is associated with an organ-specific alteration of vascular smooth muscle function that particularly affects receptor-operated contractile responses. The differential expression of this altered vascular responsiveness between organs may contribute to the observed variance in regional blood flows in sepsis.

1. Conscious, chronically-instrumented, Long Evans rats were given bolus doses of endothelin-1, endothelin-3 (both at 0.01 and 0.1 nmol kg-1), proendothelin-1 [1-38] and proendothelin-3 [1-41] (both 0.1 and 1 nmol kg-1) in order to compare their effects on coeliac haemodynamics, because it has been reported that, in conscious dogs, endothelin-1 has paradoxical, prolonged hyperaemic vasodilator effects in this vascular bed. Measurements were made also of mesenteric and hindquarters haemodynamics for comparison. In a separate experiment, endothelin-1 (0.1 nmol kg-1) was given before and 20 min after the onset of an infusion of mecamylamine (50 mumol kg h-1) to ensure that the responses measured were not confounded by rapid reflex changes in autonomic activity. 2. None of the peptides caused any increases in coeliac flow or any sustained rises in coeliac vascular conductance, although such changes were clear-cut in the hindquarters vascular bed following the higher dose of endothelin-1 and endothelin-3. In animals treated with mecamylamine the regional haemodynamic effects of the higher dose endothelin-1 were not different from those in animals with intact baroreflexes. 3. Although the lower dose of both endothelin-1 and endothelin-3 caused less marked coeliac, than mesenteric vasoconstriction, this difference was not apparent with the higher dose of the peptides, or with proendothelin-1 [1-38]. However, proendothelin-3 [1-41] had less marked coeliac and hindquarters vasoconstrictor effects than proendothelin-1 [1-38], in spite of both peptides causing similar changes in mesenteric haemodynamics.These differences could have been due to regional differences in the conversion of proendothelin-l [1-38] and proendothelin-3 [1-41] to endothelin-l and endothelin-3,respectively. Our findings contradict the proposition that exogenous proendothelin-3[1-41] is not converted into endothelin-3 in vivo.4. Since, in contrast to endothelin-1 and endothelin-3, proendothelin-1 [1-38] and proendothelin-3 [1-41] caused only small hindquarters vasodilatations, but large vasoconstrictions, it is feasible that the vasodilator responses to exogenous endothelin-l and endothelin-3 are pharmacological phenomena, and that, in vivo, the production of endothelins from proendothelins exerts widespread vasoconstrictor effects.

The ability of synthetic human calcitonin gene-related peptide (CGRP I) to act as an arterial vasodilator was tested in healthy men by measuring arterial blood flow parameters in carotid, superior mesenteric, celiac, and femoral vessels. Calculated volume flow was significantly increased (140 +/- 21% of basal) in the SMA with a 2-ng/kg/min infusion of CGRP. Carotid artery volume flow increased dose dependently (96 +/- 6%, 122 +/- 15%, 135 +/- 15% of basal, respectively, with 2, 4, or 8 ng/kg/min). With steady-state infusion, carotid and superior mesenteric arterial flow parameters remained significantly elevated for 30 minutes after cessation of peptide administration. Blood pressure was unchanged. Pulse increased dose dependently. Arterial diameters were unchanged, implying activity at the arteriolar level.

The abdominal site or sites for the satiety action of exogenous, peripherally administered bombesin (BN) were investigated. By use of a chronic arterial catheterization technique, the effects of 1, 2, and 4 micrograms/kg BN on liquid food intake of nondeprived male rats were assessed. Comparisons were made between the effects of these doses infused into the celiac or superior mesenteric arteries or injected intraperitoneally. The satiating potency of exogenous BN was significantly enhanced by direct administration into the celiac artery, which directly perfuses the stomach, pancreas, liver, spleen, and proximal duodenum. By this route, 4 micrograms/kg BN produced greater than 60% suppression of 15-min food intake. By contrast, BN infused into the superior mesenteric artery was no more effective than intraperitoneal injection. Celiac infusion of 1 micrograms/kg BN produced a suppression (30%) of intake that was equivalent to, or exceeded, that obtained after intraperitoneal injection or superior mesenteric infusion of 4 micrograms/kg. These results strongly support an upper abdominal, and possibly gastric, site for the satiety action of peripherally administered BN.

Cardiac output, ventral and dorsal aortic blood pressure, heart rate, and coeliac and mesenteric artery blood flow were recorded simultaneously in the Atlantic cod, Gadus morhua L., at rest, during exercise, during hypoxia and after feeding. In the resting unfed animals, coeliac artery blood flow was 4.1 +/- 0.8 ml min-1 kg-1 and mesenteric artery blood flow was 3.5 +/- 1.1 ml min-1 kg-1 (mean +/- S.E.M., N = 10); together, these flows represent approximately 40% of the cardiac output. Exercise or exposure to hypoxia resulted in increased visceral vascular resistance, leading to reductions in the coeliac and mesenteric artery blood flows. Coeliac and mesenteric blood flows were increased 24 h after feeding and the coeliac and systemic vascular resistances decreased in comparison with the prefeeding values. Phentolamine did not affect the gastrointestinal artery blood flow, but produced a significant decrease in the mesenteric and systemic vascular resistance. Treatment with bretylium and phentolamine revealed differences between the coeliac and the mesenteric vasculature regarding the control mechanisms during hypoxia and during exercise and feeding. During hypoxia, an adrenergic control of the gastrointestinal vasculature with both nervous and humoral components was found, whereas during exercise and after feeding an additional non-adrenergic mechanism controlling gut blood flow was demonstrated.

The role of the endothelium and vascular tone was studied on histamine-induced relaxation and contraction of the rabbit coeliac artery. Histamine contracted the tissue via the release of noradrenaline (NA), an action blocked by prazosin and mepyramine but not influenced by endothelial removal. Tachyphylaxis readily developed to histamine-induced contractions. After a moderate tone (40-55%) was induced with NA, histamine relaxed the tissues concentration-dependently. This relaxation was absent when the endothelium was removed indicating that the receptors involved are located on the endothelium. When the tone was increased to 80-85% with NA, relaxation could only be demonstrated after blocking H1-receptors. Removal of the endothelium did not influence this response. The relaxant effect of histamine in both preparations, however, was blocked by metiamide indicating that it is H2-receptor mediated. In the rabbit coeliac artery, endothelial H2-receptors are readily activated at moderate tone while muscular H2-receptors are stimulated at high tone after blocking H1-receptors. The predominance of H2-receptors in this artery may serve the physiological function of vasodilation in the blood vessels of the stomach.

The effect of glutathione (GSH) depletion on mean celiac blood flow (MCBF) was determined in domestic fowl. Diethyl maleate (DEM, 1 mL/kg body wt) decreased hepatic and duodenal GSH to approximately 15% of control. This GSH depletion was associated with an increase in MCBF and decreases in mean arterial blood pressure (MABP) and celiac vascular resistance (CVR). While indomethacin attenuated the rise in MCBF, this cyclooxygenase inhibitor had no effect on the decrease of MABP or CVR which occurred following DEM treatment. The results indicate that GSH depletion may increase vasodilatory prostaglandin synthesis since elevations in MCBF were attenuated by cyclooxygenase inhibition.

The effects on coeliac and superior mesenteric blood flows of intravenous bolus doses of arginine-8-vasopressin (0.7 and 7.0 pmol) porcine neuromedin U-25 (0.01 and 1.0 nmol), rat alpha-calcitonin gene-related peptide (0.05 and 0.5 nmol), bombesin (0.06 and 0.6 nmol), and rat corticotropin-releasing factor (1.0 and 5.0 nmol) were investigated in conscious, Long-Evans rats chronically instrumented with pulsed Doppler flow probes. The peptides investigated were chosen on the basis of the range (vasoconstrictor-vasodilator) of their effects on superior mesenteric blood flow. With the exception of rat corticotropin-releasing factor (which increased coeliac and superior mesenteric flows) all peptides caused directionally opposite changes in coeliac and superior mesenteric blood flows. The results are consistent with the proposition that endogenous neuropeptides could influence blood flows to different abdominal viscera selectively.

Pentagastrin (Peptavlon, ICI 50123) is known as a powerful stimulator of gastric acid secretion. Several authors have demonstrated a close relationship between gastric acid secretion and gastric blood flow. In this study the general hemodynamic properties of pentagastrin were investigated qualitatively and quantitatively. The study was performed on anesthetized mongrel dogs. Blood flow was assessed with non-cannulating electromagnetic flow probes. Pentagastrin was injected intravenously at intervals of 2 min in amounts between 1 ng and 8192 ng/kg, following a logarithmic scale. Pentagastrin dose-dependently increased splanchnic blood flow in a reversed U-shaped manner. The major vasoactivity occurred in two organ areas--the gastric area and the pancreatico-duodenal area. Pentagastrin increased blood flow in these areas to 300% and 350% of initial value, respectively, at a dose of 2-4 microgram/kg. Since heart rate, cardiac output, and arterial pressure were not influenced, pentagastrin had no general hemodynamic effect. This was confirmed by blood flow measurements in the renal a., common carotid a., and femoral a. It was therefore concluded that the splanchnic blood flow increase was due to an extreme decrease of splanchnic vascular resistance.

The relaxant effects of prostacyclin (PGI2) and its stable 7-oxo-analogue, a product of Chinoin Pharmaceutical Works, were compared on isolated canine cerebral, bovine coronary, rabbit coeliac and human mesenteric arterial strips. The resting tone of the coronary, cerebral and human mesenteric arteries as well as the stimulation- or noradrenaline-evoked tone of coeliac vessels were reduced by both prostanoids. The relaxant action of 7-oxo-PGI2 was slow in onset and lasted until it was washed out. The IC50 values were 4 to 40 X 10(-9) mol/l for PGI2 and 1 to 6 X 10(-7) mol/L for 7-oxo-PGI2. Compared to PGI2, 7-oxo-PGI2 was more potent in relaxing coronary arteries than the other vessels studied. Isolated tracheae from guinea-pigs were contracted by PGI2 while relaxed by 7-oxo-PGI2.

The contractile responses of the rabbit isolated coeliac and mesenteric arteries to five agonists (angiotensin, adrenaline, histamine, acetylcholine and 5-hydroxytryptamine), but not to K+, were potentiated by indomethacin (8.4 microM) The potentiation was similar whether indomethacin was added 1 h before or during the response to the agonist. The agonists that were more potentiated by indomethacin were also more dependent on the Ca2+ concentration in the medium, for their contractile action. Prostaglandin E2 in low concentrations (micromolar) did not affect the resting tone but relaxed the agonist-contracted arteries both in normal and in Ca2+-free medium. No prostaglandin E (PGE)-like substances were detected in the perfusate of arteries contracted by angiotensin. Reduction of the external Na+ concentration to 80 mM resulted in potentiation of the responses to agonists (angiotensin and adrenaline), but not to K+, and in this Na+-deficient medium potentiation by indomethacin was greatly reduced. These results suggest that potentiation by indomethacin of the arteries' responses to vasoactive substances may result from that drug's inhibitory action on sodium influx and consequent increase in calcium entry through receptor-operated channels.

1. The aim of the study was to assess and quantify any synergism occurring between the stable analogues of prostacyclin (iloprost) and nitric oxide (sodium nitroprusside) with respect to both relaxation of vascular smooth muscle and inhibition of platelet aggregation in the rabbit. 2. Iloprost (0.3-3 ng ml-1) and sodium nitroprusside (0.3-3 ng ml-1) caused dose-dependent relaxation of the rabbit mesenteric and coeliac arteries. 3. Iloprost (0.3-30 ng ml-1) and sodium nitroprusside (0.03-30 micrograms ml-1) caused dose-dependent inhibition of rabbit platelet aggregation induced by adenosine diphosphate or collagen. 4. In combination, iloprost and sodium nitroprusside caused an inhibition of platelet aggregation that was 2-3 fold greater than would be expected by summation, while no such potentiation was observed on vascular smooth muscle. 5. Thus, our results indicate that under physiological conditions the mediators prostacyclin and endothelium-derived relaxing factor (NO) can exert a synergistic action on platelets, but have only an additive effect on vascular smooth muscle.

1 Experiments have been done to study the gastric vascular response to histamine given intra-arterially in the cat.2 In experiments utilising pump perfusion of the stomach at constant flow rates, rapid intra-arterial injections of histamine elicited dose-dependent vasodilatation. The dose-response curve to histamine was displaced to the right by mepyramine and further to the right by mepyramine plus cimetidine. Cimetidine alone did not displace the histamine dose-response curve. This interaction between histamine and histamine antagonists is very similar to the interaction observed in other vascular beds.3 Intra-arterial infusions of histamine also caused vasodilatation with increased gastric blood flow, measured with an electromagnetic flow probe. Mepyramine reduced the immediate increase in blood flow during each infusion, although responses in the later stages of the infusions were unaltered. Cimetidine had no effect on the immediate response but reduced sustained responses to histamine. Treatment with mepyramine and cimetidine was required to abolish histamine responses.4 Infusions of 2-(2-aminoethyl) pyridine and dimaprit also increased gastric blood flow.5 These results indicate the involvement of both H(1)- and H(2)-receptors in histamine-induced gastric vasodilatation. There appears to be a time-base in the interaction between histamine and vascular histamine receptors; H(1)-receptor responses preceding H(2)-receptor responses.

The effects of prostaglandin synthetase inhibitors PGF2 alpha and PGI2 on the tone of isolated basilar and coeliac arteries were studied in healthy and alloxan-diabetic dogs. PGF2 alpha (1 mumol 1-1) produced a significantly higher tone in diabetic basilar arteries (1.15 +/- 0.16 mN) than in normal cerebral vessels (0.7 +/- 0.10 mN). By contrast, the contractile responses of normal and diabetic coeliac arteries to PGF2 alpha did not differ. The cyclooxygenase inhibitors indomethacin (3 mumol 1-1) and suprofen (0.58 mumol 1-1) potentiated the PGF2 alpha-evoked contractions in all of the vessels studied. The percent potentiation was greater (50-60%) in the basilar arteries from alloxan-treated dogs than in normal basilar vessels (22-30%). There was not such a difference between diabetic and normal coeliac arteries. Prostacyclin produced a concentration-related relaxation in the presence of indomethacin or indomethacin + PGF2 alpha. The relaxant potencies of PGI2 were similar in the vessels from metabolically healthy and diabetic dogs. The IC50 values for PGI2 were 11.6 +/- 1.3 and 11.8 +/- 1.8 nmol 1-1 in normal and diabetic basilar arteries, respectively; they were 25.4 +/- 3.2 and 26.2 +/- 3.9 nmol 1-1 in control and alloxan-treated coeliac vessels. These results indicate that normal and diabetic vessels may have differential reactivity to cyclooxygenase inhibitors, this difference being dependent on the vascular region.

The tripeptide ZAMI-420 has been shown by Gervasi et al. (4) to be able to prevent experimentally-induced gastric damage, possibly by interfering with the synthesis and the action of thromboxane A2 (TXA2), a potent vasoconstrictor and platelet aggregator. Further studies on a canine stomach wedge preparation, supplied with a fixed flow of 10 ml/min-1 of arterial blood from the same dog have been designed to investigate this hypothesis. Bolus injection of arachidonic acid (AA) through a 30-sec incubation coil that allows the production of TXA2 resulted in a dose-related increase in resistance to flow in the stomach wedge vasculature and blanching of the gastric mucosa. This was progressively inhibited by ZAMI-420 perfused through the delay coil. Similar results were obtained with 1-benzylimidazole (BI). ZAMI-420, but not BI, produced a partial inhibition of TXA2-induced vasoconstriction when infused close to the stomach. Investigations of the antagonistic action of ZAMI-420 on the pharmacological effect of the formed TXA2 were carried out using strips of celiac and mesenteric artery from rabbits and gastric artery from dogs. Preincubation of these vascular preparations with ZAMI-420 led to progressive inhibition of the contraction induced either by the stable endoperoxide U-46619 or by CaCl2. Whittle et al. (3) reported that TXA2 may be involved in the pathogenesis of ulcerative disorders of the stomach; if so, both the inhibition of the synthesis and the antagonism of TXA2-induced effects could be of value in the prevention of experimentally-induced gastric disorders.

Bioassays of prostacyclin by inhibition of velocity and maximum of both irreversible and biphasic platelet aggregation, and by relaxation of the potassium-contracted isolated superfused rabbit coeliac artery have been undertaken. The use of each parameter is possible within a range of PGI2 concentrations, which have been determined for each of the five parameters studied. The optimal concentrations of PGI2 for a bioassay have also been determined, corresponding to each range.

Fresh arterial tissue generates an unstable substance (prostablandin X) which relaxes vascular smooth muscle and potently inhibits platelet aggregation. The release of prostaglandin (PG) X can be stimulated by incubation with arachidonic acid or prostaglandin endoperoxides PGG2 or PGH2. The basal release of PGX or the release stimulated with arachidonic acid can be inhibited by previous treatment with indomethacin or by washing the tissue with a solution containing indomethacin. The formation of PGX from prostaglandin endoperoxides PGG2 or PGH2 is not inhibited by indomethacin. 15-hydroperoxy arachidonic acid (15-HPAA) inhibits the basal release of PGX as well as the release stimulated by arachidonic acid or prostaglandin endoperoxides (PGG2 or PGH2). Fresh arterial tissue obtained from control or indomethacin treated rabbits, when incubated with platelet rich plasma (PRP) generates PGX. This generation is inhibited by treating the tissue with 15-HPAA. A biochemical interaction between platelets and vessel wall is postulated by which platelets feed the vessel wall with prostaglandin endoperoxides which are utilized to form PGX. Formation of PGX could be the underlying mechanism which actively prevents, under normal conditions, the accumulation of platelets on the vessel wall.