Warshaw Technique in Laparoscopic Spleen-Preserving Distal Pancreatectomy: Surgical Strategy and Late Outcomes of Splenic Preservation.

Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) can be accomplished with either the preservation or the resection of splenic vessels; the latter is also known as Warshaw technique. Our study is designed to investigate the operation selection strategy when proceeding LSPDP and to evaluate the long-term outcomes of patients undergoing Warshaw surgery. The medical records and follow-up data of patients who underwent LSPDP in Qilu Hospital, Shandong University, were reviewed retrospectively. A total of thirty-five patients were involved in this study, including 17 cases of patients who were treated with Warshaw procedure (WT) while the other 18 cases had splenic vessels preserved (SVP). Compared with the SVP group, the operative time and intraoperative blood loss in WT group were improved significantly. The incidence of early postoperative splenic infarction was higher in WT group. However, there was no report of splenic abscess or second operation. Follow-up data confirmed that there was no significant difference in spleen phagocytosis and immune function compared with normal healthy population. Our study confirms that LSPDP-Warshaw procedure is a safe and efficient treatment for the benign or low grade malignant tumors in distal pancreas in selected patients. The long-term spleen function is normal after Warshaw procedure. Preoperative assessment and intraoperative exploration are recommended for the selection of operation approaches.

Splenic Artery Syndrome after orthotopic liver transplantation: a review.

Splenic Artery Syndrome (SAS) has emerged as a controversial cause for graft ischemia in orthotopic liver transplant (OLTx) recipients. A complex combination of factors including hepatic artery hypoperfusion and portal hyperperfusion can result in SAS. Clinical and laboratory findings suggest graft ischemia but are generally non-specific. Conventional angiography findings of hepatic artery hypoperfusion with early and rapid filling of the splenic artery are suggestive of the diagnosis in the appropriate clinical setting. Treatment involves proximal splenic artery embolization, surgical splenic artery ligation, or in extreme cases, splenectomy. Most patients with SAS improve clinically following treatment. However, no randomized control trials are available to compare treatment options. Identification of at risk patients with pre-operative CT scans and intra-operative ultrasound has been proposed by some and may allow for prophylactic treatment of SAS.

Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels.

German chamomile (Matricaria recutita L.), a widely-used herbal medicine, has been reported to have a wide range of biological effects, including smooth muscle relaxation. The aim of this study was to compare the effects of representative compounds from chamomile (apigenin, luteolin, (-)-α-bisabolol, farnesene, umbelliferone; 3-30 µM) on vascular tone using porcine coronary and splenic arteries mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane-mimetic U46619. Apigenin, luteolin, and (-)-α-bisabolol produced slow, concentration-dependent relaxations in both the coronary and splenic arteries that were not blocked by inhibition of nitric oxide synthase or potassium channels. Removal of extracellular calcium inhibited the relaxations to all three compounds, and these compounds also inhibited calcium re-addition-evoked contractions, indicating that the relaxation response may be mediated through inhibition of calcium influx. Apigenin and luteolin, but not (-)-α-bisabolol, enhanced the relaxation to the nitric oxide donor sodium nitroprusside, indicating that apigenin and luteolin may act to regulate cyclic GMP levels. Umbelliferone produced a rapid, transient relaxation in the splenic artery, but not the coronary artery, that was inhibited by L-NAME and removal of the endothelium, suggesting an influence on nitric oxide production. Farnesene, at concentrations up to 30 µM, was without effect in either blood vessel. In conclusion, hydroxylated compounds (apigenin, luteolin and (-)-α-bisabolol) found in chamomile all caused a slow relaxation of isolated blood vessels through an effect on calcium influx. Umbelliferone, on the other hand, produced a rapid, transient relaxation dependent upon release of nitric oxide from the endothelium.

Revisiting vascular patency after spleen-preserving laparoscopic distal pancreatectomy with conservation of splenic vessels.

BACKGROUND: We evaluated vascular patency and potential changes in preserved spleens after laparoscopic spleen-preserving distal pancreatectomy (SPDP) with conservation of both splenic vessels. METHODS: We retrospectively analyzed the patency of conserved splenic vessels in patients who underwent laparoscopic or robotic splenic vessel-conserving SPDP from January 2006 to August 2010. The patency of the conserved splenic vessels was evaluated by abdominal computed tomography and classified into three grades according to the degree of severity. RESULTS: Among 30 patients with splenic vessel-conserving laparoscopic SPDP, 29 patients with complete follow-up data were included in this study. During the follow-up period (median: 13.2 months), grades 1 and 2 splenic arterial obliteration were observed in one patient each. A total of five patients (17.2%) showed grade 1 or 2 obliteration in conserved splenic veins. Most patients (82.8%) had patent conserved splenic vein. Four patients (13.8%) eventually developed collateral venous vessels around gastric fundus and reserved spleen, but no spleen infarction was found, and none presented clinical relevant symptoms, such as variceal bleeding. There was no statistical difference in vascular patency between the laparoscopic and robotic groups (P > 0.05). CONCLUSIONS: Most patients showed intact vascular patency in conserved splenic vessels and no secondary changes in the preserved spleen after laparoscopic splenic vessel-conserving SPDP.

Pre-contraction with the thromboxane-mimetic U46619 enhances P2X receptor-mediated contractions in isolated porcine splenic artery.

We have previously demonstrated that the thromboxane-mimetic U46619 enhances α(2)-adrenoceptor-mediated contractions through increased activation of extracellular signal-regulated kinase (ERK). In this study, we determined whether U46619 also enhances P2X-mediated contractions through the same pathway. Segments of porcine splenic artery were mounted in isolated tissue baths. Tissues were pre-contracted with U46619 to 10-20% of the response to 60 mM KCl prior to addition of α,ß-methylene ATP (P2X receptor agonist). The effect of inhibition of ERK activation with the mitogen-activated protein (MAP)/ERK kinase inhibitor PD98059 (50 µM), Rho kinase inhibition with Y27632 (10 µM), p38 MAP kinase with SB203580 (10 µM) or L-type calcium channels with nifedipine (1 µM) on both the direct and enhanced contractions was then determined. U46619 enhanced the contractions to α,ß-methylene ATP. Although PD98059 inhibited the direct contractions to α,ß-methylene ATP, it had no effect on the U46619-enhanced contractions. Similarly, Y27632 and SB203580 inhibited the direct contractions to α,ß-methylene ATP, but had no effect on the enhanced contractions. Nifedipine inhibited the responses to α,ß-methylene ATP in the absence and presence of U46619. This study demonstrates that pre-contraction with U46619 enhances P2X-mediated contractions in the porcine splenic artery through a mechanism independent of ERK, Rho kinase and p38 MAP kinase. Further studies are required to determine the exact mechanism involved.

The effect of splenic arterial blood flow (SBF) on severity of hypersplenism and analysis of factors associated with SBF.

BACKGROUND: This study aims to explore the relationship between spleen arterial blood flow (SBF) with platelet count, spleen index (SPI) and the serum nitric oxide (NO) level of patients with liver cirrhosis and to investigate the role of SBF in the development of hypersplenism. METHODOLOGY: Platelet count, SPI, SBF and serum NO levels were evaluated in 100 patients with liver cirrhosis caused by hepatitis B with hypersplenism (cirrhosis group) and 30 healthy persons without hypersplenism (control group). RESULTS: Platelet count in cirrhosis group and control group was 57.0 +/- 25.6 x 109/L and 205.8 +/- 47.4 x 109/L (p = 0.000), SBF was 535.7 +/- 263.7 milmin and 172.2 +/- 66.9 ml/min (p = 0.000), and serum NO level was 98.51 +/- 23.06 micromol/L and 48.43 +/- 19.47 micromol/L (p = 0.000). Linear correlations were made between SBF and platelet count in cirrhosis group (r = -0.573, p = 0.000), SBF and SPI (r = 0.607, p = 0.01), SBF and serum NO level (r = 0.754, p = 0.000). Moreover, serum NO level increased as liver disease aggravated (82.50 +/- 15.04 pmol/L in Child grade A, 94.61 +/- 21.00 micromol/L in grade B and 116.83 +/- 18.03 micromol/L in grade C; grade A versus grade C, p = 0.003). CONCLUSION: The elevation of SBF may play an important role in the development of hypersplenism and disorders in vasoactive factors such as the serum NO caused by liver cirrhosis may play an important role in the elevation of SBF.

Splenic artery: peak systolic velocity of normal fetuses.

OBJECTIVE: To establish a reference range of splenic artery peak systolic velocity 1(SpA-PSV) in the normal singleton pregnancies (14-40 weeks). METHODS: A prospective descriptive study was conducted on uncomplicated singleton pregnancies with normal fetuses and accurate gestational age were recruited into the study. The Doppler measurements of SpA-PSV were performed by the experienced sonographers with the high-resolution machine (Aloka Prosound alpha-10, Tokyo, Japan, or Voluson E8, GE Healthcare, USA). RESULTS: A total of 540 measurements were performed, ranging from 15 to 30 for each gestational week (GA). The best regression model between GA and SpA-PSV was observed to be linear function with an equation as follows: SpA-PSV (cm/s)=-1.433+1.186 (GA, weeks) (r2=0.573). The table of nomogram for various percentile ranges was constructed. The results show a continuous increase in SpA-PSV over the period from 14 to 40 weeks. CONCLUSION: A nomogram for SpA-PSV for each GA during 14-40 weeks was constructed. This reference range may be a useful non-invasive tool in risk assessment for fetal anemia, especially due to homozygous alpha-thalassemia-1 or fetal isoimmunization.

Patency of splenic vessels after laparoscopic spleen and splenic vessel-preserving distal pancreatectomy.

BACKGROUND: This study evaluated the short- and long-term patency of preserved splenic vessels after laparoscopic spleen-preserving distal pancreatectomy (SPDP) with preservation of the splenic vessels. METHODS: This single-centre retrospective study included all patients who had undergone splenic vessel-preserving laparoscopic SPDP between 2004 and 2007. The patency of the splenic vessels was assessed by abdominal computed tomography and classified into three grades according to the degree of stenosis. RESULTS: Twenty-two patients were included. The preoperative patency of the splenic artery and vein was normal in 20 and 19 patients respectively. Normal patency of the splenic artery and vein was observed in 16 and five patients respectively within 1 month of surgery, and in 19 and nine patients 6 months or more after operation. Nine of ten patients with complete splenic vein occlusion developed a collateral circulation in the late postoperative phase. Splenic perfusion was well preserved in all patients. CONCLUSION: Splenic vessel-preserving laparoscopic SPDP has the short-term benefit of good perfusion to the spleen. In the long term, there is a risk of left-sided portal hypertension if the splenic vein becomes occluded after surgery. (c) 2009 British Journal of Surgery Society Ltd.

Fetal celiac and splenic artery flow velocity and pulsatility index: longitudinal reference ranges and evidence for vasodilation at a low portocaval pressure gradient.

OBJECTIVES: To establish longitudinal reference ranges for the fetal celiac and splenic arteries flow velocity and pulsatility index (PI), and to determine their hemodynamic relationship to venous liver perfusion and distribution and to other essential arteries. METHODS: This was a prospective longitudinal study of 161 low-risk pregnancies. Doppler recordings of the celiac and splenic arteries were made on three to five occasions at 3-5-week intervals to establish reference ranges for blood velocity and PI measurements. Peak systolic velocity in the ductus venosus, a shunt between the umbilical and inferior caval veins, was used to represent the umbilicocaval (i.e. portocaval) pressure gradient, and the left portal vein blood velocity represented the umbilical distribution to the right liver lobe. The correlations between the celiac, splenic and hepatic arteries were determined, and their association with the middle cerebral and umbilical artery PIs (MCA-PI and UA-PI) was assessed. RESULTS: Longitudinal reference ranges for the fetal celiac and splenic arteries were established based on 510 and 521 observations, respectively, during gestational weeks 21-39. Terms for calculating conditional reference ranges to be used for repeat observations are provided. Celiac and splenic artery PIs were low when portocaval pressure and umbilical supply to the right lobe were low (P < 0.0001). Their peak systolic velocity and PI were correlated (r = 0.7 (95% CI, 0.6-0.8) and r = 0.5 (95% CI, 0.3-0.6), respectively), while the PI of the hepatic artery correlated weakly with those of the celiac and splenic arteries. They were positively associated with the MCA-PI and UA-PI (P < 0.0001). CONCLUSION: We provide longitudinal reference ranges for the fetal celiac and splenic arteries Doppler measurements and show that they are involved in maintaining portal liver perfusion independently from the hepatic artery.

Effect of catheter-directed arterial embolization and laparoscopic endovascular stapling on stapled vessel integrity in a porcine model.

Arterial embolization is a frequently performed adjunctive maneuver prior to laparoscopic splenectomy or nephrectomy to facilitate laparoscopic dissection and reduce intraoperative bleeding. However, little is known regarding the effect of laparoscopic stapling across thrombosed vessels with imbedded embolic materials. This study analyzed the stapled line integrity by comparing visceral arteries treated with either platinum coils or polyvinyl alcohol (PVA) particles. Using a porcine model, 30 visceral vessels including splenic and renal arteries were treated with either coil or PVA embolization, which was followed by laparoscopic stapling. Vessel integrity and bursting pressure analysis was performed using an in vitro flow circuitry. The mean bursting pressure of the coil and the PVA group was 158 +/- 56 and 350 +/- 34 mm Hg, respectively (p < .001). The lowest bursting pressure in the coil and the PVA group was 70 and 280 mm Hg, respectively. The highest bursting pressure in the coil and the PVA group was 225 and 420 mm Hg, respectively. The bursting pressure in the splenic artery between the PVA and the coil group was 345 +/- 29 and 150 +/- 54 mm Hg, respectively (p < .001). Significant difference in the bursting pressure in the renal artery was noted in the PVA and the coil group, which was 350 +/- 40 and 160 +/- 40 mm Hg, respectively (p < .001). Our findings showed that preoperative coil embolization followed by laparoscopic vessel stapling sustained a poor busting pressure. Such a practice appears to be unsafe based on our findings and should be performed with caution in a clinical setting.

Differential arterial blood flow response of splanchnic and renal organs during low-intensity cycling exercise in women.

To investigate the regional hemodynamic responses of abdominal arteries at the onset of exercise and to focus on their transient responses, eight female subjects (21-30 yr) performed ergometer cycling exercise at 40 W for 4 min in a semi-supine position. Mean blood velocities (MBVs) in the right renal (RA), superior mesenteric (SMA), and splenic (SA) arteries were measured by pulsed echo-Doppler ultrasonography, with beat-by-beat measurements of heart rate (HR) and mean arterial pressure (MAP). The vascular resistance index (RI) of each artery was calculated from MBV/MAP. MAP (76 +/- 9 to 83 +/- 8 mmHg at 4 min) and HR (60 +/- 7 to 101 +/- 9 beats/min at 4 min) increased during exercise (P < 0.05). The MBV of RA and SA rapidly decreased after the onset of exercise (30 s; -19 +/- 5% and -19 +/- 12%, respectively), reaching -27 +/- 7% and -27 +/- 15% at the end of exercise (P < 0.05). RI did not change during the initial 30 s of exercise, reflecting a reduction in MAP, and increased toward the end of the exercise (+55 +/- 21% and +59 +/- 39%, respectively). In contrast, both the MBV and RI in the SMA remained constant throughout the exercise. The results indicate that, whereas the responses of renal and splenic vessels changed similarly throughout the protocol, the vascular response of SMA that mainly supplies blood to the intestinal tract was unchanged during exercise. We, therefore, conclude that low-intensity cycling exercise resulted in differential blood flow responses in arteries supplying the abdominal organs.

Jejunal tonometry for the diagnosis of gastrointestinal ischemia. Feasibility, normal values and comparison of jejunal with gastric tonometry exercise testing.

BACKGROUND AND AIM: In most patients with chronic splanchnic syndrome the celiac artery is involved, enabling the use of gastric exercise tonometry as a diagnostic function test. In this study, we investigated the feasibility of combining gastric and jejunal exercise tonometry and determined the normal values. We investigated the potential diagnostic value of combining gastric with jejunal exercise tonometry. MATERIALS AND METHOD: Between 1998 and 2000, combined gastric and jejunal exercise tonometry tests were performed in a healthy volunteer and in patients suspected of chronic gastrointestinal ischemia. Using automated air tonometry, gastric (PgCO2) and jejunal PCO2 (PjCO2) were measured before, during and after 10-min of exercise. Luminal-arterial PCO2 gradients (DeltagPCO2 respectively DeltajPCO2) were calculated. In the patient cohort, final diagnosis of chronic ischemia was made by our institutional multidisciplinary working group on gastrointestinal ischemia. RESULTS: Jejunal tonometry was possible in 25 of 27 participants. The healthy volunteer was tested twice, yielding a total of 26 combined tests. Mean normal basal PjCO2 was 0.9 kPa higher than PgCO2. The calculated upper threshold (mean+2SD) of normal DeltajPCO2 was 1.4 kPa. In five of eight patients with chronic gastrointestinal ischemia gastric exercise tonometry was abnormal, in one, both gastric and jejunal tonometry were abnormal, in two only jejunal exercise tonometry was abnormal. CONCLUSION: Combined gastric and jejunal exercise tonometry is a feasible procedure that is relatively easy to perform. On the basis of this pilot study, jejunal tonometry seems to have a small additional value in the diagnosis of chronic gastrointestinal ischemia.

Analysis of respiration-related movement of upper abdominal arteries: preliminary measurement for the development of a respiratory motion compensation technique of roadmap navigation.

In this study, we analyzed the respiratory motion of the upper abdominal arteries preliminary to developing a method of respiratory motion correction for the roadmap technique used in vascular interventions. We retrospectively obtained six digital angiography sequences taken during respiration. The levels of the right and left hemidiaphragms and the positions of artery bifurcation points were measured manually through each sequence. Artery bifurcation points were classified as the hepatic artery group (HAG), splenic artery group (SAG), and celiac group (CG). Correlations between the motions of each hemidiaphragm and of the artery bifurcation points in each group were determined. We found that the vertical motion of the HAG and CG matched that of the right hemidiaphragm (r = 0.924 and r = 0.888, respectively). The vertical motion of the SAG matched that of the left hemidiaphragm (r = 0.949). The mean horizontal movements for all groups were up to 1.90 mm. The vertical motion for each group matched that of the right or the left hemidiaphragm. These findings will facilitate the development of a method of respiratory motion correction for the roadmap technique.

Prostacyclin causes splenic dilation and haematological change in dogs.

1. The effect of vasodilators on spleen volume and the blood storage function is not yet well elucidated. To this end, in the present study the effects of prostacyclin, a potent vasodilator, on splenic diameter and blood cell concentrations in arterial and splenic venous blood were evaluated in anaesthetized dogs. 2. The main splenic artery and vein were dissected for measurement of splenic arterial blood flow and intra-arterial administration and for sampling of splenic venous blood, respectively. The diameter of the spleen was measured continuously by sonomicrometry. Counts of white blood cells (WBC), red blood cells (RBC) and platelets in blood sampling from the aorta and splenic vein were estimated by an automatic blood cell counter. 3. Bolus injections of prostacyclin (1-100 ng/kg) into the splenic artery produced dose-dependent increases in splenic arterial blood flow and splenic diameter associated with significant decreases in splenic venous concentrations of WBC, RBC and platelets. When splenic blood flow was kept constant, similar changes in splenic diameter and blood cell counts were observed with prostacyclin injection. 4. Splenic dilation and haematological changes induced by prostacyclin were relatively more potent than those induced by prostaglandin E(2), acetylcholine, nitroglycerin or isoproterenol when doses producing a comparable increase in splenic blood flow were compared. 5. Infusion of prostacyclin (100 ng/kg per min) into the splenic artery caused a marked increase in splenic diameter, with immediate reductions in splenic venous concentrations of WBC, RBC and platelets, followed by significant reductions in these cell counts in the general circulation. 6. These results indicate that prostacyclin produces potent and flow-independent splenic dilation that may contribute to a decrease in circulating blood cell concentrations.

Hemodynamic effects of a prostacyclin analog (Prostavasin) in systemic scleroderma patients.

PURPOSE: We examined the effects of a prostacyclin analogue (Prostavasin) on the circulation of upper extremity, cerebral, ocular and visceral districts such as portal vein, hepatic artery, superior mesenteric artery, and interlobar renal artery in scleroderma patients. MATERIALS AND METHODS: peripheral vasculature was evaluated by the brachial artery flow-mediated dilatation by the high resolution ultrasound cross-sectional measurement, splenic arterial pulsatility index (PI) resistance index (RI) of the middle cerebral artery, the central retinal artery, the visceral arteries and the portal vein flow were assessed by colour Doppler sonography in an experimental group (EG) of 50 scleroderma patients, not affected by cerebrovascular, ocular, hepatic diseases or nephropathy, before and after 3 days of Prostavasin infusion and before and after 3 days in a control group (CG) of 10 patients not receiving any treatment. RESULTS: EG patients showed significant increasement in the brachial artery flow-mediated dilatation, in the portal vein velocity and in the splenic arterial PI (pre-Prostavasin vs post-Prostavasin treatment, p < 0.001) whereas CG patients had no significant changes. Values of the middle cerebral artery, the central retinal artery, the interlobar renal artery, the superior mesenteric artery and the hepatic artery RI were reduced after treatment in the majority of EG patients although the difference did not achieve a satisfactory statistical significance. CONCLUSIONS: our results indicate that Prostavasin has a powerful effect in improving the peripheral circulation of scleroderma patients. Prostavasin significantly increases the portal vein flow but also the splenic arterial PI not supporting the hypothesis of its direct and specific action on relaxation of the hepatic micro circle.

Differences in alpha 1-adrenoceptor subtype-mediated vasoconstriction by tyramine and nerve stimulation in canine splenic artery.

This study was designed to clarify the alpha(1)-adrenoceptor subtypes mediating the vasoconstrictor response to tyramine in isolated and perfused canine splenic artery. It was shown that tyramine potentiated the nerve stimulation-induced second peaked vasoconstriction that was readily suppressed by prazosin treatment. A bolus injection of tyramine (0.01-0.3 micromol) caused a vasoconstriction in a dose-related manner. The tyramine-induced vasoconstriction was inhibited by WB 4101 (10 and 100 nM), an alpha(1A)-and alpha(1D)-adrenoceptor antagonist, in a concentration-related manner. Neither BMY 7378 (100 nM), a selective alpha(1D)-adrenoceptor antagonist, nor chloroethylclonidine (60 microM), an alpha(1B)- and alpha(1D)-adrenoceptor antagonist, affected the tyramine-induced response. The results indicate that the noradrenaline released by tyramine may diffuse to the extrajunctional cleft, and thus it activates the extrajunctional alpha(1A)-adrenoceptors, because nerve stimulation-evoked second peaked vasoconstrictions were markedly inhibited by chloroethylclonidine but not by WB 4101.

Modification of transmitter release from periarterial nerve terminals by dipyridamole in canine isolated splenic artery.

1. The aim of the present study was to determine the modulatory effects of dipyridamole on purinergic and adrenergic transmission in the canine isolated, perfused splenic artery. 2. Periarterial nerve electrical stimulation readily induced a double-peaked vasoconstriction consisting of an initial transient, predominantly P2X receptor-mediated constriction followed by a prolonged, mainly alpha1-adrenoceptor-mediated response. 3. Exposure of tissues to dipyridamole (0.1-1 micro mol/L) dose-dependently inhibited both the first and second peaks of the vasoconstrictor response at a low frequency of stimulation (1 Hz), whereas at an intermediate frequency of stimulation (4 Hz), the first peak of the response was depressed without any significant effect being observed on the second peak of constriction. 4. At a higher dose (1 micro mol/L) dipyridamole potentiated vasoconstrictor responses to noradrenaline (0.03-1 nmol). At any doses used, dipyridamole had no effect on the vasoconstrictor responses to ATP (0.03-1 micro mol). 5. Tyramine (0.01-0.3 micro mol) induced vasoconstriction in a dose-dependent manner. The dose-response curves for tyramine were shifted to the right following treatment with dipyridamole (0.1-1 micro mol/L). 6. The present results indicate that dipyridamole may inhibit purinergic and adrenergic transmission presynaptically, whereas postsynaptically dipyridamole may potentiate the adrenergic vascular constriction by inhibition of transmitter uptake.

The preferential inhibitory effect of olmesartan, a new angiotensin II type 1 antagonist, on sympathetic nerve terminals in isolated canine splenic artery.

Effects of olmesartan (RNH-6270: (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy-4-(1-hydroxy-1-methylethyl)-2-propyl[4-[2-(tetrazol-5-yl)-phenyl]phenyl]methylimidazol-5-carboxylase, an active form of olmesartan medoxomil (CS-866)) was investigated in isolated, perfused canine splenic arterial preparations. Neither exogenous noradrenaline- nor ATP-induced vasoconstrictor responses were modified by treatment with the used concentrations of olmesartan (1-100 nM). A high concentration of 10 nM angiotensin II caused a potentiation of either noradrenaline- and ATP-induced constrictions, although 1 nM angiotensin II did not induce any potentiating effects for these responses. These potentiations were inhibited by olmesartan in a concentration-related manner. Periarterial nerve electrical stimulation (PNS) readily induced a biphasic constriction consisting of an initial P2X purinoceptor-mediated vasoconstriction followed by a prolonged mainly alpha(1)-adrenoceptor-mediated response. PNS-induced 1st and 2nd peaked responses were significantly inhibited by olmesartan in a concentration-related manner. With a low concentration of 1 nM angiotensin II, which did not induce any vascular effects by itself, PNS-induced responses were markedly enhanced. The enhanced responses were inhibited by olmesartan. It is concluded that endogenous angiotensin II exerts its stimulating action on the releases of ATP and noradrenaline from the periarterial sympathetic nerve terminal, and olmesartan has an inhibitory property on angiotensin II-induced potentiation of endogenous ATP- and noradrenaline-induced responses.

Neuroeffector mechanisms involved in the regulation of dog splenic arterial tone.

It has been recognized that sympathetic neurons release several transmitters but mainly adenosine 5'-triphosphate (ATP), noradrenaline, and neuropeptide Y (NPY). Recently, we reported that periarterial nerve electrical stimulation (PNS) produced biphasic vasoconstrictions consisting of an initial transient, predominantly P2X-purinoceptor-mediated constriction followed by a prolonged, alpha(1)-adrenoceptor-mediated one in canine isolated splenic arteries. In this article, we tried to analyze the effects of several selective key drugs that influence the PNS-induced responses, and we functionally showed sympathetic transmitter releasing mechanisms by pharmacological analysis using purinergic, adrenergic, and NPYergic agonists and antagonists.