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PubMed1997

Role of extra- and intracellular Ca2+ in the lymphatic myogenic response.

We used an actively contracting in vitro preparation of bovine mesenteric lymph vessels to study the effect of selected calcium channel modulators on the ability of these vessels to propel fluid. We found that blocking the dihydropyridine receptor with nifedipine and diltiazem inhibited pumping at concentrations within the range used clinically (10(-7) and 10(-6) M, respectively). Intracellular calcium modulation using ryanodine (10(-6) M) also inhibited pumping. Furthermore, we studied the effect of these agents on the relationship between lymph flow and transmural pressure, a relationship normally described by a bell-shaped curve. Diltiazem, 10(-6) M, attenuated pumping over the range of pressures studied. On the other hand, ryanodine at 10(-7) M, a concentration capable of inhibiting pumping at a constant transmural pressure, had no effect on the pressure-flow relationship when transmural pressure was manipulated. Thus we have determined that calcium movement via the L-type channel contributes significantly to the regulation of lymph pump activity and that intracellular calcium flux plays a less significant role that may be modified by transmural pressure.

Animals↗
PubMed2002

Urea transporters are distributed in endothelial cells and mediate inhibition of L-arginine transport.

Our laboratory previously reported that uremic levels of urea inhibit L-arginine (L-Arg) transport into endothelial cells. The present study further investigated this effect. We measured L-Arg transport in cultured bovine aortic endothelial cells with normal or high urea (25 mM). The urea transport inhibitor phloretin abolished the inhibitory effect of urea on L-Arg transport, suggesting a role for urea transporters (UTs). We screened bovine aortic endothelial cells and several other endothelial cell types for the presence of UTs by using Western blot analysis. UT-B was present in all endothelial cells, irrespective of species or location of derivation, whereas UT-A distribution was variable and sparse. UT-B was also abundant in rat aorta, mesenteric blood vessels, and spinotrapezius muscle, whereas UT-A distribution was, again, variable and sparse. Chronic elevation of urea had variable, inconsistent effects on UT abundance. This study showed that urea must enter endothelial cells, probably by UT-B, to inhibit L-Arg transport. In view of the wide distribution of UT-B in rat vasculature, elevated blood urea nitrogen may lead to endothelial L-Arg deficiency in vivo.

Animals↗
PubMed1990

Lymphatic innervation.

Bovine mesenteric lymphatic vessels have nerves in their walls which in response to field stimulation cause an increase in frequency of spontaneous lymphatic contractions and this could be blocked by alpha-antagonists. When vessels were loaded with [3H]-noradrenaline, 3H-efflux was increased in response to field stimulation and this was potentiated by alpha 2-antagonists and depressed by alpha 2-agonists. Electrical activity in these vessels consisted of a single action potential which preceded each contraction. Mean resting potential was -61 mV +/- 5.7 (SD). Stimulation of postsynaptic alpha-receptors caused a depolarization accompanied by a decrease in membrane conductance while beta-receptor stimulation had the opposite effect. Lymphatic noradrenergic nerves appear to have a role in the living animal since stimulation of the sympathetic chain in anaesthetized sheep increased popliteal efferent lymph flow and this could be blocked by alpha-adrenergic blockers.

Animals↗
PubMed1990

Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term.

Our study examines the long-term cardiovascular effects after a brief period of angiotensin converting enzyme (ACE) inhibitor treatment in young spontaneously hypertensive rats (SHR). SHR were treated with perindopril (3 mg/kg/day) by gavage from 2 to 6, from 6 to 10, or from 2 to 10 weeks of age. Systolic blood pressure was measured in the tail weekly until 25 weeks of age. Corresponding control groups received distilled water for the same periods. In each treatment group blood pressure was reduced significantly during treatment, rose when treatment stopped, but plateaued significantly below control SHR thereafter. This difference in blood pressure at 25 weeks of age was due to reduced total peripheral resistance as determined by microsphere methods, but plasma renin activity and angiotensin II concentrations were not different. Cardiac hypertrophy was also reduced in treated SHR. In a separate experiment, perindopril treatment from 6 to 10 weeks of age resulted in a significant reduction in the media/lumen ratios of mesenteric resistance vessels at 32 weeks of age. Concomitant administration of angiotensin II with perindopril from 6 to 10 weeks of age not only prevented the long-term effects on blood pressure seen with perindopril treatment alone but was associated with cardiovascular hypertrophy in excess of untreated control SHR. Finally, perindopril given for a shorter period (6 to 7 weeks) or later in life (20 to 24 weeks) had no significant long-term effects on blood pressure. These results demonstrate that a 4-week period of ACE inhibitor treatment in young SHR is sufficient to prevent the full expression of genetic hypertension and cardiovascular hypertrophy and that angiotensin II might be important in the development of hypertension in this model, its role in later life being less important.

Angiotensin II↗
PubMed1991

Reducing pulse pressure in hypertension may normalize small artery structure.

To investigate the relation between the small artery structure and different blood pressure parameters, spontaneously hypertensive rats were treated from 4 to 24 weeks of age (20 weeks in total) with five different antihypertensive therapies: two angiotensin converting enzyme inhibitors (perindopril and captopril), a calcium antagonist (isradipine), a beta-blocker (metoprolol), and a vasodilator (hydralazine). At 24 weeks of age, 24-hour blood pressure was measured, and two mesenteric resistance vessels were taken from each animal. Blood pressure was 227/135 mm Hg (systolic/diastolic) and 161/106 mm Hg in untreated hypertensive and normotensive control rats, respectively. Heart rates were 376 min-1 and 295 min-1 for the two strains. All treatments reduced all blood pressure parameters except for metoprolol, which did not reduce pulse pressure. In the small arteries, the media cross-sectional area was unaffected by the treatments. When a simple correlation analysis was made, pulse pressure was found to correlate more closely (r = 0.64, p less than 0.001) to the resistance vessel media/lumen ratio than any of the other pressure parameters studied: systolic (r = 0.51, p = 0.011), mean (r = 0.41, p = 0.05), or diastolic (r = 0.28, p = 0.19). When an analysis of covariance was performed that included pulse pressure, mean blood pressure, and heart rate, which also correlated significantly to the media/lumen ratio, 81% of the variation in the media/lumen ratio could be accounted for by the variation in the three covariates (p less than 10(-5)), pulse pressure being the major factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Tyrosine kinase signaling pathways modulate angiotensin II-induced calcium ([Ca2+]i) transients in vascular smooth muscle cells.

Tyrosine kinases have been implicated in vascular smooth muscle cell proliferation and contraction. Underlying mechanisms may involve C(a2+) -dependent pathways. This study assesses relationships between angiotensin II (Ang II)-stimulated phospholipase C-mediated Ca2+ transients and tyrosine kinase-dependent pathways in vascular smooth muscle cells. Intracellular free Ca2+ concentration ([Ca2+]i) was measured in primary cultured unpassaged vascular smooth muscle cells derived from mesenteric resistance vessels of Wistar-Kyoto rats with the use of fura 2 methodology. [Ca2+]i effects of Ang II (1 nmol/L) were determined in vascular smooth muscle cells in which tyrosine kinase pathways were stimulated by insulin (70 muU/mL; 0.5 nmol/L), insulin-like growth factor-I (1 ng/mL; 0.13 nmol/L), or platelet-derived growth factor-BB (1 ng/mL; 0.04 nmol/L) and in cells in which tyrosine kinase was inhibited by specific inhibitors (1 mumol/L tyrphostin A-23 and genistein). Ang II elicited a rapid and transient [Ca2+]i response (from 94 +/- 8 to 239 +/- 5.8 nmol/L). Activation of the receptor tyrosine kinase by insulin, platelet-derived growth factor, and insulin-like growth factor-I significantly reduced (P < .01) Ang II-induced [Ca2+]i to 161 +/- 7, 189 +/- 3.7, and 183 +/- 5 nmol/L, respectively. In the presence of tyrphostin A-23 and genistein, Ang II-stimulated [Ca2+]i remained persistently elevated and failed to return to basal levels. Tyrphostin A-1, the inactive tyrphostin analogue, had not significant effect on Ang II-induced [Ca2+]i. This study demonstrates that activation of tyrosine kinase pathways reduces Ang II-elicited [Ca2+]i responses, whereas tyrosine kinase inhibition prevents [Ca2+]i recovery after agonist stimulation. Interaction between tyrosine kinase- and phospholipase C-dependent signaling pathways modulates vascular smooth muscle cell [Ca2+]i responses to Ang II.

Angiotensin II↗
PubMed1979

The influence of blood flow on temperature distribution in the exteriorized mouse intestine during treatment by hyperthermia.

The non-uniform effects of hyperthermia observed in mouse intestine when heating is achieved by immersion of an exteriorized loop of jejunum in a hot bath were quantified. Intestinal damage was assayed by crypt destruction and correlated with local temperature and distance from major mesenteric blood vessels. The rate of rise of temperature during heating was much greater in regions far from blood vessels than in those close to vessels. Equilibrium temperatures in regions close to vessels were as much as 2 degrees C below liquid bath temperature. Such temperature differentials agreed well with those predicted from the heterogeneity observed in crypt destruction. Both histological and thermometric data suggest that major blood vessels may influence tissue temperature over a distance of approximately 2 mm and, within this region, temperature gradients of 1 degree C per mm may exist. These findings raise questions concerning the interpretation of previously reported data from water-bath heating of both tumours and normal tissues. They also emphasize the need for consideration of the influence of blood flow on heating patterns during hyperthermal treatment of patients.

Animals↗
PubMedDate not supplied

A reassessment of the treatment of salicylate poisoning.

The treatment of salicylate poisoning is based on the prevention of further absorption, and enhancement of excretion of already absorbed drug. A variety of methods based on this rationale have been used over the years. One of the more popular and successful treatments has been forced alkaline diuresis to encourage excretion. This technique, however, is not without risk and has now been replaced with alkalinisation alone, which has been shown to be safer and equally successful. The use of activated charcoal as an acute absorbing agent for drug still in the upper gastrointestinal tract is beneficial in minimising further absorption. A recent development in the use of activated charcoal is the administration of multiple doses which are believed to enhance elimination of absorbed drug. The charcoal adsorbs salicylate diffusing back into the gut from the coeliac and mesenteric blood vessels thereby effectively eliminating it--a form of 'internal peritoneal dialysis'. Multiple-dose activated charcoal and alkalinisation are currently the most popular methods of treatment.

Drug Overdose↗
PubMed1992

Age-related decrease of neurogenic release of calcitonin gene-related peptide from perivascular nerves in spontaneously hypertensive rats.

Changes in the neurogenic release of calcitonin gene-related peptide (CGRP) by perivascular nerve stimulation (PNS) were investigated in perfused mesenteric vascular beds isolated from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). CGRP-like immunoreactivity (CGRP-LI) in the perfusate was examined by radioimmunoassay (RIA) and identified to be CGRP itself by combined analysis with radioimmunoassay and HPLC. In SHR and WKY preparations, PNS (4 and 8 Hz) evoked a frequency-dependent increase of CGRP-LI in the perfusate, which was abolished by 500 nM tetrodotoxin and the removal of Ca2+ from the medium. In young SHR and WKY (8-week-old), there was no significant difference in the release of CGRP-LI induced by PNS, whereas the release in the 15-week-old SHR was significantly less than in the 15-week-old WKY and in 8-week-old SHR. These results suggest that neural release of CGRP from perivascular nerves in mesenteric resistance vessels of SHR decreases with age.

Aging↗
PubMed1999

Characterization of a transformed ovine lymphatic endothelial cell line.

OBJECTIVE: To develop a non-tumor-derived stable lymphatic endothelial cell line that exhibits rapid growth rate without serum and exogenous growth factors, while still maintaining key features characteristics of the non-transformed lymphatic endothelium. METHODS: Lymphatic endothelial cells were isolated from ovine mesenteric lymphatic vessels, grown to confluence and transfected with SV40 DNA using the calcium phosphate method. The resulting cell line was characterized using morphological, immunocytochemical, flow cytometric analysis, and immunoprecipatitation and Western blotting methods. RESULTS: The resulting cell line (sheep lymphatic endothelial transformed cell line, SLET-1) underwent rapid proliferation in the absence of growth factors and reduced concentrations of serum. In addition, key morphological and functional properties of the non-transformed lymphatic endothelium were retained. These include the ability to form confluent monolayer cultures, the expression of the lymphatic endothelial-specific VEGFR-3, FLT-4) tyrosine kinase receptor, the biosynthesis and secretion of von Willebrand factor and plasminogen activators. In addition, SLET-1 cells express cell surface antigens found on LEC that may act as antibody targets in various immune reactions. Monolayer cultures of the SLET-1 cells incubated with endothelial cell-growth factor formed tubular structures, indicating the retention of the capacity to differentiate. CONCLUSION: The SLET-1 cell line retained key morphological and functional properties characteristic of the non-transformed lymphatic endothelium. The ability to form capillary-like tubular structures provides an important cell line for defining the role of specific proteins that are involved in the lymphagiogenic (formation of new lymphatic vessels) process. Thus, this transformed lymphatic endothelial cell line provides an in citro model that may have widespread utility in studying regulatory mechanisms of lymphatic endothelial cell function and differentiation.

Animals↗
PubMed1999

[Our experience with the use of Absolok polydioxanone resorbable clips in laparoscopic surgery].

BACKGROUND: The study aims to evaluate the efficacy of resorbable clips in polydioxanone in laparoscopic surgery. METHODS: The authors report their personal experience regarding the use of Absolok (ABL) resorbable clips in laparoscopic surgery. Out of a total of 745 laparoscopic operations performed from September 1992 to February 1997, 438 included the use of resorbable clips in place of metal clips, both for cystic duct section during cholecystectomy and vascular structures, or to lock continuous sutures. ABL clips were also used for major vessels (e.g. mesenteric artery) during laparoscopic colic resections. RESULTS: In all cases when they were used, ABL never gave rise to complications, such as biliary outflow or hemorrhage caused by the dislocation of the clips themselves. CONCLUSIONS: The authors conclude by affirming the value and safety of this type of clip.

Humans↗
PubMed1999

Chyloperitoneum and abdominal adhesions in a miniature horse.

Chyloperitoneum is a potential cause of colic in horses. Although rare in horses, chyloperitoneum can develop secondary to tearing of mesenteric adhesions and rupture of mesenteric lymphatic vessels. The prognosis for horses with chyloperitoneum depends on the underlying cause and the response to treatment.

Abdomen↗
PubMedDate not supplied

[Adenocarcinoma of the duodenojejunal flexure. A report of 2 clinical cases and a review of the literature].

The authors report two cases of adenocarcinoma of the duodenojejunal angle and remark the rarity of this pathology, the difficulty of making diagnosis peculiar to neoplasm of the small intestine and the difficulty of treatment peculiar to tumours of the duodenum. According to the literature the diagnosis was determined through X-ray films, after traditional endoscopy was inadequate. Surgical treatment is radical, with extensive exeresis procedures (unless the mesenteric upper vessels are infiltrated) since the prognosis of this tumours is good.

Adenocarcinoma↗
PubMed1999

Effects of perindopril, propranolol, and dihydrochlorothiazide on cardiovascular remodelling in spontaneously hypertensive rats.

AIM: To investigate the effects of perindopril, propranolol, and dihydrochlorothiazide on artery wall thickening, left ventricular hypertrophy, and cardiac fibrosis in spontaneously hypertensive rats (SHR). METHODS: After measurement of systolic blood pressure (SBP), 16-wk-old Male SHR were randomly divided into 3 groups (each n = 10), given perindopril (Per, 5 mg.kg-1.d-1), propranolol (Pro, 40 mg.kg-1.d-1), dihydrochlorothiazide (DCT, 100 mg.kg-1.d-1) respectively by gavage for 12 wk. Sex-, age-, and number-matched untreated SHR and normotensive Wistar Kyoto rats (WKY) served as controls. When the treatment finished, body weights (BW) and SBP were measured before decapitation of the rats. The heart was excised rapidly, the left ventricle was weighed and then subjected to collagen content analysis. Vascular wall and lumen ratio from aorta, renal arteries and branch III vessels of mesenteric arteries were determined morphometrically. RESULTS: Treated rats in 3 groups showed a lower SBP and the ratio of left ventricle weight to body weight (LVW/BW) compared with WKY. Artery wall thickening was similarly inhibited in the treated groups. Per and Pro inhibited cardiac fibrosis, but collagen concentration increased in DCT treated SHR [collagen volume fraction (CVF): 19 +/- 4 vs SHR 14 +/- 4, P < 0.05; perivascular collagen fraction(PVCF): 84 +/- 7 vs SHR 79 +/- 5, P < 0.05]. CONCLUSION: Per and Pro inhibited, but DCT promoted, cardiac fibrosis.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Acute effects of peritoneal dialysis on hemodynamics.

OBJECTIVES: To investigate the acute hemodynamic effects of peritoneal dialysis (PD) using the noninvasive Portapres technique [TNO Biomedical Instrumentation (TNO BMI); Amsterdam, The Netherlands]. DESIGN AND METHODS: Blood pressure was measured in 21 consecutive patients on continuous ambulatory PD during a standard peritoneal permeability analysis (SPA). Blood pressure, stroke volume, cardiac output, and total peripheral resistance were recorded and calculated using continuous finger pressure recordings with Portapres and Modelflow software (TNO BMI). The SPA consists of four phases: (1) drainage of night dwell dialysate, (2) instillation of a rinsing solution (1.36% glucose), (3) drainage of rinsing solution, and (4) instillation of the test solution (3.86% glucose to which dextran 70 has been added). RESULTS: Both systolic blood pressure (SBP) (7 +/- 9 mmHg, p < 0.005) and diastolic blood pressure (DBP) (5 +/- 6 mmHg, p < 0.01) increased during phase 2. Systolic BP and DBP increased further during phase 4 (SBP 8 +/- 14 mmHg, p < 0.05; DBP 6 +/- 8 mmHg, p < 0.005). These BP increases were caused by a rise in total peripheral resistance of 10% +/- 18% (p< 0.05) during phase 1, and 15% +/- 21% (p < 0.005) during phase 2. CONCLUSIONS: Instillation and dwell of a dialysis solution during PD causes a rise in blood pressure. This is caused by an increase in total peripheral resistance. Factors influencing total peripheral resistance could be a direct mechanical effect of dialysate on mesenteric resistance vessels or a temperature-related effect.

Adult↗
PubMed2001

[Pancreatic hormone amylin and integrity of the gastric mucosa].

The paper presents experimental findings of some possible mechanisms of protective antiulcerous action of amyline. Amyline is the second beta-cell pancreatic hormone, which has been just recently discovered. The authors have studied the effects of amyline on gastric secretion, mast cell functions, mesenteric lymphatic microvascular contractility, i.e. on individual aggressive and protective factors of the gastric mucosa. Amyline has been found to inhibit basal acid gastric secretion and the secretion stimulated by vagal irritation. The peptide reduces the secretory activities of mast cells. Amyline given to animals increases the heparin saturation index of mast cells and decreases the degranulation index. Amyline-induced stabilization of mast cells appears to followed by the decreased release of histamine and other damaging substances. The stimulating effect of amyline on the contractile activity of mesenteric lymphatic vessels was recorded in rats. Amyline increases both the frequency and amplitude of their contractions. The increased lymph flow that is closely associated with microcirculation promotes the maintenance of tissue homeostasis. Therefore, the protective antiulcerous properties of amyline reduce the action of aggressive agents on the gastric mucosa and stimulate protective ones.

Amyloid↗