Anthocyanins Activate Membrane Estrogen Receptors With Nanomolar Potencies to Elicit a Nongenomic Vascular Response Via NO Production.

Background The vascular pharmacodynamics of anthocyanins is only partially understood. To examine whether the anthocyanin-induced vasorelaxation is related to membrane estrogen receptor activity, the role of ERα or GPER antagonism was ascertained on anthocyanins or 17-ß estradiol-(E2) induced vasodilatations and NO production. Methods and Results The rat arterial mesenteric bed was perfused with either anthocyanins or corresponding 3-O-glycosides, or E2, to examine rapid concentration-dependent vasorelaxations. The luminally accessible fraction of NO in mesenteric perfusates before and after anthocyanins or E2 administration was quantified. Likewise, NO-DAF signal detected NO production in primary endothelial cells cultures incubated with anthocyanins or E2 in the absence and presence of ERα (ICI 182,780) or GPER (G-36) selective antagonists. Anthocyanins or corresponding glycosides elicited, within minutes, vasodilation with nanomolar potencies; half maximal anthocyanin response reached 50% to 60% efficacy, in contrast to acetylcholine. The vasorelaxation is of rapid onset and exclusively endothelium-dependent; NOS inhibition annulled the vasorelaxation. The delphinidin vascular response was not modified by 100 nmol/L atropine but significantly attenuated by joint application of ICI plus G-36 (52±4.6 versus 8.5±1.5%), revealing the role of membrane estrogen receptors. Moreover, the anthocyanin or E2-induced NO production was antagonized up to 70% by these antagonists. NO-DAF signal elicited by anthocyanins was annulled by NOS inhibition or by ICI plus G-36 addition. Conclusions The biomedical effect of anthocyanins or 3-O-glycosylates derivatives contained in naturally purple-colored foods or berries is due to increased NO production, and not to the phytochemical's antioxidant potential, highlighting the nutraceutical role of natural products in cardiovascular diseases.

Magnesium lithospermate B protects the endothelium from inflammation-induced dysfunction through activation of Nrf2 pathway.

Magnesium lithospermate B (MLB) is an active component of Salvia miltiorrhiza Radix, a traditional Chinese herb used in treating cardiovascular diseases. In this study, we investigated the protective effects of MLB against inflammation-induced endothelial dysfunction in vitro and in vivo, and the underlying mechanisms. Endothelial dysfunction was induced in human dermal microvascular endothelial cells (HMEC-1) in vitro by lipopolysaccharide (LPS, 1 µg/mL). We showed that pretreatment with MLB (10-100 µM) dose-dependently inhibited LPS-induced upregulation of inflammatory cytokines ICAM1, VCAM1, and TNFα, which contributed to reduced leukocytes adhesion and attenuation of endothelial hyperpermeability in HMEC-1 cells. SD rats were injected with LPS (10 mg/kg, ip) to induce endothelial dysfunction in vivo. We showed that pretreatment with MLB (25-100 mg/kg, ip) dose-dependently restored LPS-impaired endothelial-dependent vasodilation in superior mesenteric artery (SMA), attenuated leukocyte adhesion in mesenteric venules and decreased vascular leakage in the lungs. We further elucidated the mechanisms underlying the protective effects of MLB, and revealed that MLB pretreatment inhibited NF-κB activation through inhibition of IκBα degradation and subsequent phosphorylation of NF-κB p65 in vitro and in vivo. In HMEC-1 cells, MLB pretreatment activated the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. Knockdown of Nrf2 with siRNA abolished the inhibitory effects of MLB on IκBα degradation and ICAM1 up-regulation, which were mimicked by PKC inhibition (Gö6983) or PI3K/Akt inhibition (LY294002). In summary, our results demonstrate that MLB inhibits NF-κB activation through PKC- and PI3K/Akt-mediated Nrf2 activation in HMEC-1 cells and protects against LPS-induced endothelial dysfunction in murine model of acute inflammation.

Beneficial Effects of Adrenal Androgen Supplement in Bleeding Cirrhotic Rats.

Critical illness is accompanied by hypothalamic-pituitary-adrenal axis activation, but adrenal insufficiency characterized by inadequate glucocorticoid synthesis is common in critically ill cirrhotic patients, the "hepato-adrenal syndrome." Adrenal cortex also synthesizes androgen (dehydroepiandrosterone, DHEA). DHEA maintains microcirculation by enhancing vascular endothelial nitric oxide synthase (eNOS) activity. In critical patients of other disease entities, a shift of adrenal steroidogenesis away from androgens toward glucocorticoid has been noted, arousing interests in androgen replacement in critical settings. Nevertheless, this has not been surveyed in cirrhosis with hemorrhage. In this study, liver cirrhosis was induced with common bile duct ligation (BDL) in Spraque-Dawley rats. Sham rats were controls. DHEA or vehicle was injected at the beginning of hemorrhage-transfused procedure, followed by terlipressin injection. Hemodynamic parameters were measured. Then abdominal aorta, superior mesenteric arteries (SMA) and splenorenal shunt (prominent portosystemic collateral vessel in rodents) eNOS and inducible NOS protein expressions were evaluated. In bleeding BDL groups without terlipressin injection, adrenocorticotropic hormone (ACTH) stimulation test was performed to evaluate the DHEA response. The results showed that DHEA significantly elevated mean arterial pressure, cardiac output, and stroke volume of bleeding cirrhotic rats treated with terlipressin and reduced systemic vascular resistance without affecting SMA flow, resistance, and portal pressure. DHEA upregulated abdominal aorta and SMA eNOS expressions. ACTH did not stimulate DHEA synthesis in bleeding BDL rats. In conclusion, androgen deficiency exists in bleeding cirrhotic rats. DHEA augments terlipressin-induced amelioration of shock without influencing splanchnic hemodynamics, possibly rendering it a feasible adjunct to vasoconstrictors in variceal hemorrhage.

Total flavonoids from Astragalus alleviate endothelial dysfunction by activating the Akt/eNOS pathway.

Objective To investigate the vasodilative and endothelial-protective effects and the underlying mechanisms of total flavonoids from Astragalus (TFA). Methods The vasodilative activities of TFA were measured with a myograph ex vivo using rat superior mesenteric arterial rings. The primary human umbilical vein endothelial cell (HUVEC) viabilities were assayed using the cell counting kit-8 after hypoxia or normoxia treatment with or without TFA. Akt, P-Akt, eNOS, P-eNOS, Erk, P-Erk, Bcl-2 and Bax expression were analyzed using western blotting. Results TFA showed concentration-dependent vasodilative effects on rat superior mesenteric arterial rings, but had no effects on normal or potassium chloride precontracted arterial rings. TFA did not affect HUVEC viabilities in normoxia, but dramatically promoted cell proliferation in the concentration range of 1 to 30 µg/mL under hypoxia. Moreover, TFA significantly increased the ratios of P-Akt/Akt and P-eNOS/eNOS in vascular endothelial cells under hypoxic conditions, but did not change the P-Erk/Erk or Bcl-2/Bax ratios. Conclusions TFA might exhibit vasorelaxant and endothelial-protective effects via the Akt/eNOS signaling pathway.

The renal effects of droxidopa are maintained in propranolol treated cirrhotic rats.

BACKGROUND & AIMS: Droxidopa improves hemodynamic and renal alterations of cirrhotic rats without changing portal pressure. We aimed to evaluate the effects of a combined treatment with droxidopa and non-selective beta-blockers or statins in order to decrease portal pressure, while maintaining droxidopa beneficial effects. METHODS: Acute studies combining droxidopa with carvedilol, propranolol or atorvastatin in four-week bile-duct ligated (BDL) rats and a chronic study combining propranolol and droxidopa for 5 days in CCl4 -cirrhotic rats were performed. Hemodynamic values were registered and biochemical parameters from blood and urine samples analyzed. RESULTS: Bile-duct ligated rats treated with carvedilol + droxidopa showed no changes in mean arterial pressure (MAP) and portal pressure (PP) compared to vehicles. Atorvastatin + droxidopa combination also failed to reduce PP, but maintained the beneficial increase in MAP and superior mesenteric artery resistance (SMAR) and decrease in blood flow (SMABF) caused by droxidopa. In contrast, the acute administration of propranolol + droxidopa significantly reduced PP maintaining a mild increase in MAP and improving, in an additive way, the decrease in SMABF and increase in SMAR caused by droxidopa. This combination also preserved droxidopa diuretic effect. When chronically administered to CCl4 -cirrhotic rats, propranolol + droxidopa caused a decrease in PP, a significant reduction in SMABF and an increase in SMAR. The combination did not alter liver function and droxidopa diuretic and natriuretic effect, and even improved free water clearance. CONCLUSION: Droxidopa could be effective for the renal alterations of cirrhotic patients on propranolol therapy and the combination of both drugs may balance the adverse effects of each treatment.

Effect of plant polyphenols on ischemia-reperfusion injury of the isolated rat heart and vessels.

In the present study, we investigated the potential protective effect of selected natural substances in a rat model of heart and mesenteric ischemia-reperfusion (I/R). Experiments were performed on isolated Langendorff-perfused rat hearts, subjected to 30-min global ischemia, followed by 30-min reperfusion. Arbutin, curcumin, rosmarinic acid and extract of Mentha x villosa were applied in the concentration of 1 × 10⁻5 mol/l 10 min before the onset of ischemia and during reperfusion, through the perfusion medium. Mesenteric ischemia was induced by clamping the superior mesenteric artery (SMA) for 60 min, subsequent reperfusion lasted 30 min. Production of reactive oxygen species (ROS) by SMA ex vivo was determined by luminol-enhanced chemiluminiscence (CL). The effect of the substances was tested after their incubation with tissue. Curcumin and extract of Mentha x villosa were found to be the most effective in reducing reperfusion-induced dysrhythmias--ventricular tachycardia and fibrillation. This effect was accompanied by bradycardic effect. The mesenteric I/R induced an increase in CL in vascular tissue which was dampened by substances tested. All substances tested were found to have antioxidant properties, as demonstrated by a reduction in ROS production in mesenteric vessels. This effect was confirmed in curcumin and extract of Mentha x villosa which reduced reperfusion dyshythmias.

The effect of warming of the abdomen and of herbal medicine on superior mesenteric artery blood flow - a pilot study.

BACKGROUND: In traditional Japanese and Chinese medicine, warming the abdomen with moxibustion or herbal medicines has been used for various diseases. However, the effects of these therapies on hemodynamics have not been clear. We clarify the physiological effects of these therapies on the superior mesenteric artery (SMA) blood flow. PARTICIPANTS AND METHODS: 28 healthy male volunteers were randomly assigned to groups A and B. Group A (n = 14) underwent local thermal stimulation of the paraumbilical region for 20 min at a temperature of 40 °C; this simulated the heat and mechanical pressure effects of moxibustion. Group B (n = 14) took the herbal medicine Daikenchuto (TJ-100; 5.0 g) with distilled water. As a control, group C (n = 14) took distilled water alone. Blood flow volume in the SMA was measured by ultrasound from rest to 50 min after the start of each intervention. RESULTS: The SMA blood flow volume increased significantly between 10 to 40 min after the start of thermal stimulation (p < 0.05), and it also increased significantly between 10 to 50 min after administration of TJ-100 (p < 0.01) as compared to the resting volume. However, SMA blood flow volume did not change significantly after administration of water alone. There was no significant difference in SMA blood flow changes between groups A and B. CONCLUSIONS: The results suggest that one of the physiological effects of warming the abdomen according to a traditional concept in thermal stimulation and herbal medicine is an increase of SMA blood flow volume.

Vasodilator effect of Cassiarin A, a novel antiplasmodial alkaloid from Cassia siamea, in rat isolated mesenteric artery.

The aim of this study was to investigate the vasorelaxant effect induced by cassiarin A, a novel antiplasmodial alkaloid from Cassia siamea, in rings cut from rat superior mesenteric arteries. In rings precontracted with phenylephrine, cassiarin A induced a concentration-dependent relaxation. This relaxation was attenuated: 1) after removal of the endothelium or after pretreatment of rings with 100 microM of N(G)-nitro-L-arginine (nitric oxide synthase inhibitor) or 10 microM of 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (guanylyl cyclase inhibitor), but not after pretreatment with 10 microM of indomethacin (cyclooxygenase inhibitor); and 2) after pretreatment of preparations with either a nonselective or selective inhibitor of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels [1 mM of tetraethylammonium or 100 nM of iberiotoxin, respectively]. The cassiarin A-induced relaxation was also attenuated by these BK(Ca) inhibitors in endothelium-denuded preparations. The cassiarin A-induced relaxation was not altered by treatment with the ATP-sensitive K(+)-channel inhibitor glibenclamide (10 microM) or with the voltage-dependent K(+)-channel inhibitor 4-aminopyridine (1 mM). In isolated mesenteric artery rings, cassiarin A tended to increase nitric oxide (NO) levels. These results suggest that in the rat mesenteric artery, cassiarin A-induced relaxation may be mediated by endothelial NO and may occur partly via BK(Ca)-channel activation.

Cardiovascular effects induced by Cymbopogon winterianus essential oil in rats: involvement of calcium channels and vagal pathway.

OBJECTIVES: This study has investigated the cardiovascular effects of the Cymbopogon winterianus essential oil (EOCW) in rats. C. winterianus is a plant used in folk medicine for the treatment of hypertension. METHODS: For the measurement of haemodynamic and ECG parameters, male Wistar rats under anaesthesia were cannulated in the abdominal aorta and lower vena cava and electrodes were subcutaneously implanted in their paws. For an in-vitro approach, the rats were killed and the superior mesenteric artery was removed and cut into rings (1-2 mm). These rings were then mounted in organ baths containing Tyrode's solution at 37 degrees C and gassed with carbogen. KEY FINDINGS: In rats, EOCW (1-20 mg/kg, i.v.) induced dose-dependent hypotension and tachycardia. These effects were not affected by L-NAME or indometacin, but were partially reduced after atropine administration. EOCW (20 mg/kg only) also induced bradycardia-associated sinoatrial blockade, junctional rhythm, and first-degree atrioventricular block, which was abolished after atropine administration or vagotomy. In arterial rings, EOCW (0.1-3000 microg/ml) induced relaxation of phenylephrine tonus that was not affected by removal of the endothelium. These relaxations were similar to those observed in rings without endothelium precontracted with KCl 80 mm. EOCW was able to antagonize the CaCl(2) (30-300 mum) induced contractions in depolarizing solution (KCl 60 mm). CONCLUSIONS: These results demonstrated that EOCW induced hypotension and vasorelaxation. These effects appeared to be mainly mediated by Ca(+2)-channel blocking. Furthermore, the higher dose of EOCW induced transient bradycardia and arrhythmias due to a cardiac muscarinic activation secondary to a vagal discharge.

The herbal medicine Daikenchuto increases blood flow in the superior mesenteric artery.

Daikenchuto is a traditional herbal medicine that is used for the treatment of cold feeling in the abdomen, while Orengedokuto, also a traditional herbal medicine, is used for treating inflammatory and ulcerative diseases affecting internal organs. However, the effects of these herbal medicines on cardiac output (CO) and intestinal blood flow have never been investigated. This examiner-blinded randomized crossover study intended to clarify the influence of Daikenchuto and Orengedokuto on CO and blood flow volume in the superior mesenteric artery (SMA). Fourteen healthy men (35 +/- 7 years old) were randomly assigned to two groups: group A and group B. Initially, all subjects were given 50 ml of water orally. After 7 days, subjects in group A were given 5.0 g of Daikenchuto, and 7 days later they were given 2.5 g of Orengedokuto. These herbal medicines were given to group B subjects in the reverse order. CO and SMA blood flow volume were measured from rest to 90 min after the administration of water or each medicine. There was a significant increase in SMA blood flow volume after the administration of Daikenchuto, compared to water alone (p < 0.05) and Orengedokuto (p < 0.05). SMA blood flow volume was significantly increased between 5 and 90 min after administration of Daikenchuto (p < 0.01) compared to the resting state. However, there was no significant change in CO after the administration of either agent. The present study indicates that Daikenchuto increases SMA blood flow volume without increasing CO.

Involvement of Na(+)-Ca (2+) exchanger in the endothelium-independent vasorelaxation induced by Curcuma longa L. in isolated rat superior mesenteric arteries.

Previous studies confirmed that the methanolic extract from Curcuma longa L. (CLME) lowers arterial blood pressure and heart rate in rats due to the blockade of extracellular Ca(2+) influx. The aim of this study was to investigate the involvement of Na(+)-Ca (2+) exchanger in the vasorelaxant effects elicited by CLME in isolated rat superior mesenteric arteries. CLME (1-1,000 microg/ml) concentration-dependently relaxed phenylephrine (PHE) (10 microM) pre-contracted arterial rings with intact-endothelium (pD(2) and E(max) = 2.04 +/- 0.06 and 88.3 +/- 3.2%) or denuded-endothelium (pD(2) and E(max) = 2.06 +/- 0.03 and 91.4 +/- 1.0%), respectively, suggesting that the removal of endothelium has no significant effect (P>0.05) on the vasorelaxation induced by CLME. Furthermore, CLME (30, 100 and 300 microg/ml) inhibited the cumulative concentration-response curves to PHE (10(-8)-10(-5) M) in a concentration-dependent manner, whereas, treatment with ouabain 100 microM (selective blocker of Na(+)-K(+) ATPase) has no effect on the relaxant responses of CLME. However, treatment with nickel chloride (NiCl(2)) (100, 300 and 400 microM), a putative Na(+)-Ca(2+) exchanger inhibitor, concentration-dependently reduced the vasorelaxant responses of CLME. Precisely, NiCl(2) at 100, 300 and 400 microM significantly (P<0.05) decreased the pD(2) and E(max) values of CLME (1.86 +/- 0.03 and 81.3 +/- 1.2%, 1.77 +/- 0.03 and 60.2 +/- 0.8%, 1.69 +/- 0.04 and 55.3 +/- 1.6%, respectively). Also, CLME (100 microg/ml) produced less relaxant effect with decreasing extracellular Na(+) concentration. CLME-induced vasorelaxation was completely abolished in a Na(+)-free Tyrode's solution, a condition that eliminates the influence of the forward mode of the exchanger. The results provide indirect evidence that the stimulation of the forward mode of Na(+)-Ca (2+) exchanger may probably contribute to the vasorelaxation induced by CLME in endothelium-denuded arterial rings.

Cardiovascular effects of the aqueous extract from Caesalpinia ferrea: involvement of ATP-sensitive potassium channels.

Caesalpinia ferrea is a plant very used in the folk medicine for treatment of several diseases, such as diabetes. This study investigated the cardiovascular effects of the aqueous extract from stem bark of C. ferrea (AECF). In non-anesthetized rats, AECF (10, 20, 40, 60 and 80 mg/kg; i.v.) induced hypotension (-9+/-1;-12+/-1;-14+/-1; -20+/-3 and -51+/-6%; respectively) and tachycardia (6+/-1; 8+/-1; 12+/-2; 14+/-2 and 26+/-3%; respectively). Hypotension was not affected after atropine or L-NAME. Furthermore, AECF (40 mg/kg) induced atrioventricular block and extrasystoles, which was not affected after atropine. In intact rings of the rat mesenteric artery, AECF (0.001-30 mg/ml, n=6) induced relaxations of phenylephrine tonus (Emax=110+/-4%), which was not changed after the removal of endothelium (Emax=113+/-9%). In rings without endothelium pre-contracted with KCl 80 mM, phenylephrine plus KCl 20 mM or phenylephrine plus glibenclamide, the curve to AECF was significantly attenuated (Emax=24+/-4%, 70+/-5% and 62+/-7%, respectively, n=6), but was not affected in the presence of tetraethylammonium or 4-aminopyridine (Emax=125+/-15% and 114+/-7%, respectively, n=6). These results demonstrate that AECF induces hypotension associated to tachycardia; however, in dose of 40 mg/kg, AECF induces transient bradyarrhythmias. Furthermore, AECF induces vasodilatation in rat mesenteric artery which appears to be mediated by ATP-sensitive K+ channel openings.

Effect of noise on microvascular integrity in laboratory rats.

Housing rats in an environment with high personnel activity increases microvascular leakiness to albumin in the mesenteric microcirculation and causes mast cell degranulation. In this study, rats were exposed to daily 15-min episodes of 90-dB SPL noise to determine whether similar effects occurred and whether vitamin E with a-lipoic acid or Traumeel (a homeopathic anti-inflammatory-analgesic) reduced these effects. Groups of rats fed a control diet (1000 IU/kg vitamin E) only, the control diet with Traumeel, or a diet with 10,000 IU/kg vitamin E and 1.65 g/kg lipoic acid were exposed to daily noise for 3 to 5 wk; a fourth group of rats, fed control diet, was housed with no excess noise. The rats were anesthetized, the superior mesenteric artery cannulated, and a portion of the microvasculature perfused for 1 min with fluoroscein isothiocyanate-albumin before fixing for microscopy. All groups exposed to excess noise had significantly more leaks per venule length and greater leak area per venule length than did the quiet group. However, the number and area of leaks in the rats that received Traumeel or vitamin E were significantly smaller than those in rats exposed to noise only. In addition, mast cell degranulation was significantly lower in rats given Traumeel. Thus exposure of rats to excessive noise produces structural damage in the mesenteric microvasculature that is significantly reduced by dietary supplements.

Endothelium-derived factors and k+ channels are involved in the vasorelaxation induced by Sida cordifolia L. in the rat superior mesenteric artery.

The vasorelaxantion of the aqueous fraction of the hydroalcoholic extract of the Sida cordifolia leaves (AFSC) was evaluated in this work. In rat superior mesenteric artery, AFSC (3-1000 microg/mL) induced relaxation of phenylephrine-induced contractions. This effect was significantly attenuated after removal of the endothelium, after atropine (1 microM), L-NAME (100 microM), indomethacin (10 microM), high K+ (20 mM), tetraethylammonium (1 microM), a K(Ca) blocker, apamin (1 microM), a SK(Ca) blocker and ChTX (0.1 microM), a BK(Ca) blocker, however, it was not affected after glibenclamide (10 microM), an KATP blocker, and 4-aminopyridine (1 microM), a Kv blocker. ChTX (0.1 microM) was able to induce an additional inhibition of the vasorelaxation induced by AFSC in the presence of L-NAME plus indomethacin. The vasorelaxation induced by AFSC in the presence of L-NAME plus indomethacin plus ChTX was not different from that induced by AFSC in rings without endothelium. In conclusion, the results show that endothelium-derived factors (mainly NO, PGI2) and K+ channels (BK(Ca) and SK(Ca)) play a crucial role in the vasorelaxation induced by AFSC in the rat superior mesenteric artery.

Antihypertensive and vasodilator effects of methanolic and aqueous extracts of Tribulus terrestris in rats.

The effects of methanolic and aqueous extracts of Tribulus terrestris on rat blood pressure (BP) and the perfused mesenteric vascular bed were investigated. The extracts dose-dependently reduced BP in spontaneously hypertensive rats (SHRs) with the aqueous fraction being more potent than the methanolic fraction at all doses tested. In vitro, the methanolic but not aqueous extract produced a dose-dependent increase in perfusion pressure of the mesenteric vascular bed. When perfusion pressure was raised with phenylephrine (10(-5) M), the aqueous extract produced a dose-dependent reduction in perfusion pressure at all doses. A low dose of the methanolic extract produced a vasoconstrictor effect while higher doses produced dose-dependent reduction in perfusion pressure. L-NAME (10(-4) M) significantly reduced but did not abolish vasodilation induced by the extracts. Vasodilator responses to aqueous and methanolic fractions were significantly reduced in preparations where perfusion pressure was raised with KCl (60 mM). A combination of KCl and L-NAME abolished the vasodilator responses induced by the extracts. It was concluded that methanolic and aqueous extracts of Tribulus terrestris possess significant antihypertensive activity in spontaneously hypertensive rats. The antihypertensive effects appeared to result from a direct arterial smooth muscle relaxation possibly involving nitric oxide release and membrane hyperpolarization.

Effect of enteral supplementation with glutamine on mesenteric blood flow in premature neonates.

BACKGROUND AND AIMS: This study investigated the effects of enterally supplied glutamine on mesenteric blood flow in premature neonate. METHODS: Twenty-five neonates, aged at least 14 days and free of acute illness participated in a prospective, randomised, double-blind study. All were fed with total enteral nutrition enriched with glutamine (0.7 g kg(-1)day(-1), group 1) or isonitrogenous control (group 2). Blood flow velocities in the superior mesenteric artery were analysed by pulsed Doppler US before and after 21 days of supplemented feeding. Peak systolic velocity (PSV), end-diastolic velocity (EDV) and time-averaged mean velocity (TAV) were measured and resistance index (RI) and flow (Q) were calculated. RESULTS: Both groups were well matched clinically at inclusion. At inclusion, the velocimetry parameters were (mean +/- SD) : PSV:114.9 +/- -38 cms(-1), EDV:17.5 +/- 7.5 cm x s(-1), TAV:44.8 +/- 18.2 cms(-1), RI : 0.8 +/- 0.1, Q : 2.4 +/- 1.2 mls(-1). Mesenteric blood flow parameters remained stable between day 0 and day 21 with same values in both groups. CONCLUSIONS: Superior mesenteric blood flow remained stable in neonates after 14 days of life and did not appear to be influenced by enteral glutamine at that stage.

Antihypertensive, vasodilator and antioxidant effects of a vinifera grape skin extract.

Cumulative evidence suggests that moderate wine consumption exerts a cardioprotective effect. We investigated the occurrence of an antihypertensive effect of an alcohol-free hydroalcoholic grape skin extract (GSE) obtained from skins of a vinifera grape (Vitis labrusca) in experimental rodent hypertension models. The vasodilator effect of GSE (polyphenols concentration 55.5 mg g(-1)) was also assessed in the isolated mesenteric vascular bed of Wistar rats and the antioxidant effect was studied on lipid peroxidation of hepatic microsomes. Oral administration of GSE significantly reduced systolic, mean and diastolic arterial pressure in Wistar rats with desoxycorticosterone acetate-salt and N(G)-nitro-L-arginine methyl ester (L-NAME) induced experimental hypertension. In the rat isolated mesenteric vascular bed pre-contracted with norepinephrine, bolus injections of GSE induced endothelium-dependent vasodilatation that was substantially inhibited by L-NAME, but not by indometacin, tetraethylammonium or glibenclamide. Lipid peroxidation of hepatic microsomes estimated as malondialdehyde production was concentration-dependently inhibited by GSE. In conclusion, the antihypertensive effect of GSE might be owing to a combination of vasodilator and antioxidant actions of GSE. These findings also suggest that the beneficial effect of moderate red wine consumption could be owing to an antihypertensive action induced by compounds occurring in the skin of vinifera grapes.

Hemodynamic effects of Salvia miltiorrhiza on cirrhotic rats.

Salvia miltiorrhiza (Sm) administration has been shown to reduce hepatic fibrosis in rats. We investigated the hemodynamic effects of Sm on bile duct ligated (BDL) rats. Hemodynamic, histological, and vascular contractile studies were conducted in rats 4 weeks after bile duct ligation. An aqueous extract of Sm (0.2 g twice per day) or vehicle was administered for 4 weeks to BDL rats. Sm treatment in BDL rats significantly reduced histological grades of fibrosis and ameliorated the portal hypertensive state (including portal venous pressure, superior mesenteric artery blood flow, cardiac index, and total peripheral resistance) as compared with vehicle treatment. Moreover, Sm treatment enhanced the vascular sensitivity of mesenteric arteries to phenylephrine in BDL rats. Sm treatment had no effect on plasma biochemical profiles of either BDL or normal rats. Our results suggest that 4-week Sm treatment ameliorates the portal hypertensive state in BDL rats.

Effect of triglycerides with different fatty acid chain length on superior mesenteric artery blood flow.

Fat stimulates superior mesenteric artery (SMA) blood flow. Little is known, however, about the influence of fatty acid chain length on SMA flow. The present study was performed to compare the effect of long chain triglycerides (LCT, corn oil), very long chain triglycerides (VLCT, fish oil) and medium chain triglycerides (MCT) on SMA flow. A total of seven healthy volunteers (four men, three women; aged 26 +/- 4 years) participated in three experiments, performed in random order during 60 min continuous intra-duodenal infusion of either LCT (30 mL h(-1); 240 kcal h-1), equicaloric VLCT (30 mL h(-1); 240 kcal h(-1)) or MCT in equimolar (15 mL h(-1); 113 kcal h(-1)) and equicaloric amount (30 mL h(-1); 225 kcal h(-1)). Basal and stimulated SMA blood flow were measured by Doppler ultrasonography. At regular intervals blood samples were taken for measurement of plasma cholecystokinin (CCK) and plasma peptide YY (PYY). Basal SMA blood flow volumes were not significantly different among the LCT, VLCT and MCT experiments (426 +/- 135, 460 +/- 114 and 503 +/- 177 mL min(-1), respectively). The SMA flow increased significantly (P < 0.05) during fat infusion but was significantly higher during LCT (1460 +/- 692 mL min-1) compared with VLCT (1061 +/- 384 mL min-1), MCT 15 mL h(-1) (870 +/- 286 mL min(-1)) and MCT 30 mL h-1 (904 +/- 223 mL min(-1)). Plasma CCK levels increased significantly (P < 0.05) during LCT and VLCT but not during MCT infusion. No correlation was found between SMA flow and plasma CCK levels (r = 0.27; P = 0.2) The SMA blood flow in response to triglycerides is dependent on fatty acid chain length. This chain length-dependent blood flow response is, however, not linear and is not related to plasma CCK levels.

Acute abdomen during adjuvant chemotherapy: superior mesenteric artery thrombosis associated with CMF chemotherapy.

We report a case of superior mesenteric artery thrombosis in a 57-year-old woman undergoing chemotherapy for T1N1M0, breast cancer. Although cancer itself is associated with an increased risk of thrombotic events, treatment with chemotherapy and/or tamoxifen in breast cancer patients increases this risk. Most cases reported are of venous thromboembolism; arterial events are rare.