Intrauterine growth restriction-induced deleterious adaptations in endothelial progenitor cells: possible mechanism to impair endothelial function.

Intrauterine growth restriction (IUGR) can induce deleterious changes in the modulatory ability of the vascular endothelium, contributing to an increased risk of developing cardiovascular diseases in the long term. However, the mechanisms involved are not fully understood. Emerging evidence has suggested the potential role of endothelial progenitor cells (EPCs) in vascular health and repair. Therefore, we aimed to evaluate the effects of IUGR on vascular reactivity and EPCs derived from the peripheral blood (PB) and bone marrow (BM) in vitro. Pregnant Wistar rats were fed an ad libitum diet (control group) or 50% of the ad libitum diet (restricted group) throughout gestation. We determined vascular reactivity, nitric oxide (NO) concentration, and endothelial nitric oxide synthase (eNOS) protein expression by evaluating the thoracic aorta of adult male offspring from both groups (aged: 19-20 weeks). Moreover, the amount, functional capacity, and senescence of EPCs were assessed in vitro. Our results indicated that IUGR reduced vasodilation via acetylcholine in aorta rings, decreased NO levels, and increased eNOS phosphorylation at Thr495. The amount of EPCs was similar between both groups; however, IUGR decreased the functional capacity of EPCs from the PB and BM. Furthermore, the senescence process was accelerated in BM-derived EPCs from IUGR rats. In summary, our findings demonstrated the deleterious changes in EPCs from IUGR rats, such as reduced EPC function and accelerated senescence in vitro. These findings may contribute towards elucidating the possible mechanisms involved in endothelial dysfunction induced by fetal programming.

Intrauterine growth restriction increases circulating mitochondrial DNA and Toll-like receptor 9 expression in adult offspring: could aerobic training counteract these adaptations?

It has been demonstrated that intrauterine growth restriction (IUGR) can program increase cardiometabolic risk. There are also evidences of the correlation between IUGR with low-grade inflammation and, thus can contribute to development of several cardiometabolic comorbidities. Therefore, we investigated the influence of IUGR on circulating mitochondrial DNA (mtDNA)/Toll-like receptor 9 (TLR9) and TNF-α expression in adult offspring. Considering that the aerobic training has anti-inflammatory actions, we also investigated whether aerobic training would improve these inflammatory factors. Pregnant Wistar rats received ad libitum or 50% of ad libitum diet throughout gestation. At 8 weeks of age, male offspring from both groups were randomly assigned to control, trained control, restricted and trained restricted. Aerobic training protocol was performed on a treadmill and after that, we evaluated circulating mtDNA, cardiac protein expression of TLR9, plasma and cardiac TNF-α levels, and left ventricle (LV) mass. We found that IUGR promoted an increase in the circulating mtDNA, TLR9 expression and plasma TNF-α levels. Further, our results revealed that aerobic training can restore mtDNA/TLR9 content and plasma levels of TNF-α among restricted rats. The cardiac TNF-α content and LV mass were not influenced either by IUGR or aerobic training. In conclusion, IUGR can program mtDNA/TLR9 content, which may lead to high levels of TNF-α. However, aerobic training was able to normalize these alterations. These findings evidenced that the association of IUGR and aerobic training seems to exert an important interaction effect regarding pro-inflammatory condition and, aerobic training may be used as a strategy to reduce deleterious adaptations in IUGR offspring.

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice.

The recently described 'gasomediator' hydrogen sulfide (H2S) has been involved in pain mechanisms, but its effect on pruritus, a sensory modality that similarly to pain acts as a protective mechanism, is poorly known and controversial. The effects of the slow-releasing (GYY4137) and spontaneous H2S donors (Na2S and Lawesson's reagent, LR) were evaluated in histamine and compound 48/80 (C48/80)-dependent dorsal skin pruritus and inflammation in male BALB/c mice. Animals were intradermally (i.d.) injected with C48/80 (3µg/site) or histamine (1µmol/site) alone or co-injected with Na2S, LR or GYY4137 (within the 0.3-100nmol range). The involvement of endogenous H2S and KATP channel-dependent mechanism were also evaluated. Pruritus was assessed by the number of scratching bouts, whilst skin inflammation was evaluated by the extravascular accumulation of intravenously injected 125I-albumin (plasma extravasation) and myeloperoxidase (MPO) activity (neutrophil recruitment). Histamine or C48/80 significantly evoked itching behavior paralleled by plasma extravasation and increased MPO activity. Na2S and LR significantly ameliorated histamine or C48/80-induced pruritus and inflammation, although these effects were less pronounced or absent with GYY4137. Inhibition of endogenous H2S synthesis increased both Tyrode and C48/80-induced responses in the skin, whereas the blockade of KATP channels by glibenclamide did not. H2S-releasing donors significantly attenuate C48/80-induced mast cell degranulation either in vivo or in vitro. We provide first evidences that H2S donors confer protective effect against histamine-mediated acute pruritus and cutaneous inflammation. These effects can be mediated, at least in part, by stabilizing mast cells, known to contain multiple mediators and to be primary initiators of allergic processes, thus making of H2S donors a potential alternative/complementary therapy for treating inflammatory allergic skin diseases and related pruritus.

Proposal of a histopathological predictive rule for the differential diagnosis between American tegumentary leishmaniasis and sporotrichosis skin lesions.

BACKGROUND: American tegumentary leishmaniasis (ATL) and sporotrichosis exhibit similar histopathology and low frequencies of microorganism detection. OBJECTIVES: This study seeks to identify microscopic alterations that can distinguish between these diseases. METHODS: Haematoxylin and eosin stained slides of 171 ATL and 97 sporotrichosis samples from active cutaneous lesions were examined for histopathological alterations. The lesions were diagnosed by isolating the agent (which was not visible) in culture. An intuitive diagnosis was assigned to each slide. The strength of the association between the histopathological findings and the diagnosis was estimated by an odds ratio, and each finding was graded according to a regression model. A score was assigned to each sample based on the histopathological findings. A study of the interobserver reliability was performed by calculating kappa coefficients of the histopathological findings and intuitive diagnoses. RESULTS: The markers 'macrophage concentration', 'tuberculoid granuloma' and 'extracellular matrix degeneration' were associated with ATL. 'Suppurative granuloma', 'stellate granuloma', 'different types of giant cells', 'granulomas in granulation tissue' and 'abscess outside the granuloma' were associated with a diagnosis of sporotrichosis. 'Macrophage concentration' and 'suppurative granuloma' had the highest (substantial and almost perfect, respectively) reliability. The regression model score indicated 92.0% accuracy. The intuitive diagnosis had 82.5% diagnostic accuracy and substantial reliability. CONCLUSIONS: Taking into account the clinical and epidemiological context, some histopathological alterations might be useful for the differential diagnosis between ATL and sporotrichosis cutaneous lesions in cases in which the aetiological agent is not visible.

Second-trimester soft markers: relation to first-trimester nuchal translucency in unaffected pregnancies.

OBJECTIVE: Genetic sonography following first-trimester combined screening appears to increase substantially detection rates for Down syndrome but it relies on the unproved assumption of independence between these tests. In this study we aimed to investigate the relationship between first-trimester nuchal translucency (NT) and a series of second-trimester soft markers and structural defects in unaffected pregnancies. METHODS: NT measurement in the first trimester was followed by second-trimester scan (18 to 23 + 6 weeks) including examination for three categorical markers (intracardiac echogenic foci, hyperechogenic bowel and structural defects) and measurement of nasal bone length, nuchal-fold thickness, femur length, humerus length, renal pelvis diameter and prenasal thickness. All continuous variables were expressed in multiples of the median (MoM) for gestation and correlation coefficients between log-transformed NT and second-trimester variables were calculated. In addition, frequencies of soft markers and structural defects in cases with increased NT were compared to those with normal NT, using MoM cut-offs. RESULTS: In a dataset of 1970 cases, NT was significantly correlated (P < 0.05) with all second-trimester continuous variables, the correlation being strongest for nuchal-fold thickness (r = 0.10). There was a higher frequency of cases with second-trimester nuchal-fold thickness above the 97.5(th) centile (10.7 vs. 2.2%) and hyperechogenic bowel (2.4 vs. 0.1%) in cases with increased NT. CONCLUSIONS: Straightforward reassessment of risk using likelihood ratios derived from the second-trimester genetic sonogram might lead to inaccurate estimates. Multivariate models using continuous second-trimester variables might be preferable in sequential screening strategies.

Amplifying the benefits of agroecology by using the right cultivars.

Tropical soils are particularly vulnerable to fertility losses due to their low capacity to retain organic matter and mineral nutrients. This urges the development of new agricultural practices to manage mineral nutrients and organic matter in a more sustainable way while relying less on fertilizer inputs. Two methods pertaining to ecological engineering and agroecology have been tested with some success: (1) the addition of biochar to the soil, and (2) the maintenance of higher earthworm densities. However, modern crop varieties have been selected to be adapted to agricultural practices and to the soil conditions they lead to and common cultivars might not be adapted to new practices. Using rice as a model plant, we compared the responsiveness to biochar and earthworms of five rice cultivars with contrasted selection histories. These cultivars had contrasted responsivenesses to earthworms, biochar, and the combination of both. The mean relative increase in grain biomass, among all treatments and cultivars, was 94% and 32%, respectively, with and without fertilization. Choosing the best combination of cultivar and treatment led to a more than fourfold increase in this mean benefit (a 437% and a 353% relative increase in grain biomass, respectively, with and without fertilization). Besides, the more rustic cultivar, a local landrace adapted to diverse and difficult conditions, responded the best to earthworms in terms of total biomass, while a modern common cultivar responded the best in term of grain biomass. This suggests that cultivars could be selected to amplify the benefit of biochar- and earthworm-based practices. Overall, selecting new cultivars interacting more closely with soil organisms and soil heterogeneity could increase agriculture sustainability, fostering the positive feedback loop between soils and plants that has evolved in natural ecosystems.

Predicting preterm delivery in asymptomatic patients with prior preterm delivery by measurement of cervical length and phosphorylated insulin-like growth factor-binding protein-1.

OBJECTIVE: To evaluate the efficacy of cervical length measurement in combination with a bedside assessment of phosphorylated insulin-like growth factor-binding protein-1 (phIGFBP-1) as a predictor of preterm delivery in asymptomatic pregnant women with a history of preterm birth. METHODS: Cervical length was measured using transvaginal sonography at 22-24 weeks of gestation in 105 singleton pregnancies and a rapid strip test was performed to detect phIGFBP-1 in cervical secretions from 24 to 34 weeks. Receiver-operating characteristics (ROC) curves were constructed to compare the performance of phIGFBP-1 at different gestational ages, and cervical length at 22-24 weeks, in predicting preterm delivery. RESULTS: The rate of spontaneous delivery before 37 and 34 weeks was 23.8% and 11.4%, respectively. Women with cervical lengths less than 20 mm had a risk of spontaneous preterm delivery before 34 and 37 weeks of 43.5% and 69.6%, respectively. The performance of phIGFBP-1 levels as a predictor of preterm delivery was significantly higher when the test was carried out at 30 weeks' gestation. Cervical assessment in combination with phIGFBP-1 at 30 weeks had the steepest ROC curve (area under the curve=0.93; 95% CI, 0.88-0.98, P<0.001). CONCLUSION: Both cervical length and phIGFBP-1 measurement are useful in the prediction of preterm delivery in patients with a history of preterm birth and the combined method of measuring cervical length at 22-24 weeks and phIGFBP-1 at 30 weeks improves upon either method used alone.

Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo.

In the present study, we investigated the potentiating effect of angiotensin-(1-7) [Ang-(1-7)] on bradykinin (BK)-induced vasodilation in the mesenteric vascular bed of anesthetized spontaneously hypertensive rats using intravital microscopy. Topical application of BK and Ang-(1-7) induced vasodilation in mesenteric arterioles. The BK-induced effect, but not acetylcholine, sodium nitroprusside, or histamine responses, was potentiated in the presence of Ang-(1-7). This interaction was abolished by BK-B(2) and Ang-(1-7) antagonists (HOE 140 and A-779, respectively), a K(+) channel blocker (tetraethylammonium), and cyclooxygenase inhibitors (indomethacin and diclofenac); however, nitric oxide synthase inhibition (Nomega-nitro-L-arginine methyl ester) did not modify the Ang-(1-7)-potentiating activity. Long-term angiotensin-converting enzyme (ACE) inhibition increased BK and Ang-(1-7)-induced vasodilation. The BK potentiation by Ang-(1-7) was preserved after ACE inhibition, Ang II type 1 receptor blockade, or the combination of both treatments. The most striking finding of this study was the unexpected observation that the potentiation of BK vasodilation in spontaneously hypertensive rats treated short- or long-term with ACE inhibitors was reverted by the Ang-(1-7) antagonist A-779. Our results unmasked a key role for an Ang-(1-7)-related mechanism in mediating BK potentiation by ACE inhibitors.

Aspartic protease in leaves of common bean (Phaseolus vulgaris L.) and cowpea (Vigna unguiculata L. Walp): enzymatic activity, gene expression and relation to drought susceptibility.

Four cultivars of related species, common bean and cowpea, which exhibit different degrees of drought resistance, were submitted to water stress by withholding irrigation. Drought induced an increase in endoproteolytic activity, being higher in susceptible cultivars (bean) than in tolerant ones (cowpea). An aspartic protease activity was found to be strongly induced especially in bean. From a cowpea leaf cDNA library, a full length aspartic protease precursor cDNA was obtained. Transcript accumulation in response to water stress indicated that the expression of the gene was constitutive in cowpea and transcriptionally up-regulated in bean. The results showed that drought-tolerant and drought-susceptible bean plants differ regarding aspartic protease precursor gene expression.

Deoxycorticosterone acetate-salt hypertensive rats display gender-related differences in ET(B) receptor-mediated vascular responses.

1. Male DOCA-salt rats exhibit vasoconstriction upon ET(B) activation. Because hypertension is less severe in female than male DOCA rats, we hypothesized that female DOCA rats would display attenuated ET(B) vasoconstrictor responses. 2. Uninephrectomized Wistar rats received DOCA and drinking water containing NaCl/KCl. Control rats received vehicle and tap water. Systolic blood pressure was higher in male vs female DOCA rats. Responses to endothelin-1 (ET-1), IRL-1620, an ET(B) agonist, and acetylcholine were evaluated in isolated aortas and in vivo in the mesenteric microcirculation. 3. Endothelium-denuded aortas from male, but not female, DOCA rats displayed increased sensitivity to ET-1. IRL-1620 contracted aortas from male DOCA rats, but not control or female DOCA aortas. Noradrenaline-constricted and endothelium-intact aortas from male, but not female, DOCA rats displayed increased relaxation to IRL-1620 compared to control aortas. 4. In vivo, increased vasoconstriction to ET-1 was observed in male and female DOCA rats. IRL-1620 induced vasodilation in control rats, but vasoconstriction in male DOCA rats. There were minimal changes in diameter in vessels from female DOCA rats. 5. The initial fall in blood pressure induced by ET-1 and IRL-1620 was attenuated in male DOCA rats. Bosentan, a mixed ET(A)/ET(B) receptor antagonist, lowered blood pressure in male and female DOCA rats, but a greater and marked decrease occurred in the male DOCA group. 6. The gender-related differences in ET-1/ET(B)-mediated effects both in the vasculature and blood pressure suggest that sex-related functional up-regulation of ET(B) receptors may play a role in the more severe hypertension in male DOCA hypertensive rats.

Synergistic effect of angiotensin-(1-7) on bradykinin arteriolar dilation in vivo.

The interaction between angiotensin [Ang-(1-7)] and bradykinin (BK) was determined in the mesentery of anesthetized Wistar rats using intravital microscopy. Topical application of BK and Ang-(1-7) induced vasodilation that was abolished by the BK B2 receptor antagonist HOE-140 and the Ang-(1-7) antagonist A-779, respectively. BK (1 pmol)-induced vasodilation, but not SNP and ACh responses, was potentiated by Ang-(1-7) 10 pmol and 100 pmols. The effect of 100 pmol of Ang-(1-7) on BK-induced vasodilation was abolished by A-779, indomethacin, and L-nitroarginine methyl esther, whereas losartan was without effect. Enalaprilat treatment enhanced the BK- and Ang-(1-7)-induced vasodilation and the potentiating effect of Ang-(1-7) on BK vasodilation. The potentiation of BK-induced vasodilation by Ang-(1-7) is a receptor-mediated phenomenon dependent on cyclooxygenase-related products and NO release.

Increased acetylcholine-induced vasodilation in pregnant rats: A role for gap junctional communication.

We have tested the hypothesis that increased gap junctional communication contributes to the augmented endothelium-dependent vasodilation in pregnancy. Contractile force and connexin43 expression were measured in aortic rings from nonpregnant and pregnant rats. Norepinephrine-constricted aortas from pregnant rats were more sensitive to acetylcholine, but not to sodium nitroprusside, compared with those from nonpregnant rats. Vessels from pregnant rats, constricted either with 45 mmol/L KCl or with norepinephrine + 10(-4) mol/L N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase, also exhibited greater relaxation to acetylcholine. Heptanol, an uncoupler of gap junctional communication, inhibited acetylcholine responses in norepinephrine-constricted aortas from nonpregnant rats but greatly impaired acetylcholine relaxation in aortas from pregnant rats. Heptanol also inhibited in both groups acetylcholine responses in vessels constricted with KCl, only minimally affected acetylcholine relaxation in arteries constricted with norepinephrine + L-NMMA, and did not change sodium nitroprusside-induced relaxation. Tetraethylammonium chloride induced greater contractions in control aortas compared with aortas from pregnant rats. Increased connexin43 mRNA levels were found in the uterus and in the mesenteric, uterine, and thoracic aortic arteries, but not in the heart and brain, from pregnant rats. These results suggest that increased gap junctional communication, possibly due to increased gap junction protein expression, may facilitate the effects of endothelium-derived relaxing factors, contributing to the augmented endothelium-dependent relaxation in arteries from pregnant rats.

Induction of acute and chronic pancreatitis with the use of the toxin of the scorpion Tityus serrulatus: experimental model in rats.

We observed that the purified venom of the Tityus serrulatus scorpion (T1 fraction), injected i.v. in rats, in a single dose of 0.5 mg/kg, produces: acute pancreatitis, characterized by degranulation and acinar cell vacuolization, necrosis and an inflammatory reaction, 24, 48 and 96 hours after the injection; chronic pancreatitis, characterized by interstitial fibrosis, lymphocyte infiltration, ductal and ductular dilation, acinar cell atrophy, periductal ductular hyperplasia, 20 days after injection: hyperplasia of Langerhans' islets and nesidioblastosis, associated to chronic pancreatitis. The absence of deaths in the experimental group is an interesting finding: the dose used preserved the animals from death and allowed the safe follow-up of the progression of the provoked pancreatitis. The results led us to conclude that the toxin of Tityus serrulatus scorpion is an agent of considerable efficacy in the induction of pancreatitis in rats providing an experimental model of acute and chronic form of this disease.

Spontaneously hypertensive versus control rat aorta response to neutrophil-derived factors.

We designed experiments to study the interaction of activated rat peritoneal neutrophils with aortas from spontaneously hypertensive rats (SHR) compared with those from normotensive rats. In aortic rings precontracted with phenylephrine, neutrophils obtained from normotensive rats caused a cell number-dependent relaxation of normotensive rat aorta with or without endothelium, whereas relaxation (at lower concentrations) followed by contraction (at higher concentrations) was observed in SHR aorta with endothelium. In SHR aortic rings denuded of endothelium, neutrophils did not induce contraction. The relaxation might be due to a factor indistinguishable from nitric oxide. The contraction might be due to prostaglandin H2 because it was blocked by indomethacin, a cyclooxygenase inhibitor, and ridogrel, a thromboxane A2 synthetase inhibitor/thromboxane A2-prostaglandin H2 antagonist, but not by superoxide dismutase, a superoxide anion scavenger, or dazoxiben, a thromboxane A2 synthetase inhibitor. SHR neutrophils caused a cell number-dependent relaxation of normotensive rat aorta with or without endothelium, whereas relaxation followed by contraction was observed in SHR aorta with endothelium. In SHR aortic rings denuded of endothelium, neutrophils did not induce contraction. The relaxation might be due to a factor indistinguishable from nitric oxide. The contraction seems to be due to superoxide anion because it was inhibitable by indomethacin and superoxide dismutase but not by dazoxiben and ridogrel. Equivalent amounts of superoxide anion were produced by unstimulated and phorbol myristate acetate-stimulated neutrophils obtained from either SHR or normotensive rats. Therefore, increased production of this anion could not explain the contraction observed in hypertensive aortas.(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelium inactivation in in vitro perfused vascular beds. Comparison of methods.

In order to choose the best procedure to inactive the endothelium from vascular beds perfused in vitro, we compared four methods: perfusion with sodium deoxycholate 0.3% for 30 sec; 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate 0.3% (CHAPS) for 2.5 min; collagenase 0.2% for 15 min, and distilled water for 10 min, using the mesenteric arterial bed (MAB) of the rat. The effectiveness of the treatments used to inactivate the endothelium was assessed functionally by using acetylcholine and sodium nitroprusside and histologically using light microscopy. Phenylephrine was used to test the contractile properties of the preparations after each treatment. After collagenase, distilled water, and CHAPS treatment, a potentiated response to phenylephrine was observed, whereas sodium deoxycholate treatment did not modify phenylephrine-induced responses. Acetylcholine-induced responses were reduced by collagenase (60% reduction), CHAPS (30% reduction), and distilled water (52% reduction) treatment, and sodium deoxycholate completely abolished acetylcholine-induced responses. Except after collagenase treatment, smooth muscle relaxant responses were not altered. Medial smooth muscle cells displayed an unchanged morphology, appearing similar to those in control mesenteric arterial beds, except for collagenase and distilled water. Despite the fact that sodium deoxycholate treatment completely abolished acetylcholine-induced response, endothelial cells were still found. No treatment totally removed endothelial cells. In conclusion, we suggest that sodium deoxycholate treatment is the best procedure to inactivate endothelial cells from vascular beds perfused in vitro since it completely abolished endothelium-dependent relaxation and did not interfere with smooth muscle vasodilating and contracting properties.

Effect of indomethacin on the microvessel reactivity of two-kidney, one-clip hypertensive rats.

Endothelial cells modulate vascular tone by releasing endothelium-derived relaxing and contracting factors. An imbalance of these factors in hypertension could contribute to increased peripheral vascular resistance. To investigate whether an endothelium-derived contracting factor is involved in the altered reactivity of microvessels of two-kidney, one-clip hypertensive rats, mesenteric arterioles either perfused in vitro or studied in vivo were used. In two-kidney, one-clip hypertensive rats, a potentiation to noradrenaline was observed in preparations tested either in vitro or in vivo. Indomethacin treatment did not correct the increased response to noradrenaline in microvessel preparations. Thus the involvement of an endothelium-derived contracting factor which is sensitive to indomethacin blockade, could be discarded. A decreased response to acetylcholine, an endothelium-dependent vasodilator, was observed in in vitro and in vivo preparations. The responses to sodium nitroprusside, an endothelium-independent vasodilator, were not altered in microvessel preparations of hypertensive rats. In two-kidney, one-clip hypertensive preparations, indomethacin normalized the endothelium-dependent relaxations. Relaxations to sodium nitroprusside were not altered by indomethacin. It is suggested that endothelium-dependent relaxations are impaired in two-kidney, one-clip hypertension because of a cyclooxygenase-dependent substance interfering with the release and/or action of endothelium-dependent relaxing factor.

Enhancement of aorta tonus evoked by hypertonic solutions is endothelium-dependent.

1. The effect of NaCl hypertonic solutions on the contractions induced by noradrenaline or prostaglandin F2 alpha and on the relaxant effect of acetylcholine and sodium nitroprusside was investigated in aortae with or without endothelium isolated from rats. 2. Hypertonic solutions enhanced the contractions elicited by the vasoconstrictor agents in preparations with endothelium and this phenomenon was not altered by previous treatment of the animals with reserpine or the preparations with methylene blue or indomethacin. 3. In hypertonic medium acetylcholine but not sodium nitroprusside vasodilator effect was inhibited. 4. We suggest that NaCl hypertonic solutions modify vascular reactivity probably through: (i) the release of an endothelium-derived contracting factor not sensitive to cyclooxygenase inhibitors; (ii) a diminished release of an endothelium-derived relaxing factor not related to the cGMP system.

Indirect evidence for an endothelium-derived contracting factor released in arterioles of deoxycorticosterone acetate salt hypertensive rats.

In order to investigate if endothelium-derived contracting factor (EDCF) is involved in the altered reactivity of microvessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats, mesenteric arterioles, either perfused in vitro or studied in vivo in situ, were used. The responses to norepinephrine, acetylcholine, sodium nitroprusside and papaverine were studied in animals treated with indomethacin. Norepinephrine was equally effective in evoking a constrictor response in the in vitro perfused arteriolar bed of DOCA-salt hypertensive and control rats. A potentiation to this agent was, however, observed in preparations tested in vivo in situ. A decreased response to acetylcholine, an endothelium-dependent vasodilator, was observed in perfused in vitro and in vivo in situ preparations. The responses to sodium nitroprusside, an endothelium-independent agent, in microvessel preparations of hypertensive rats, and the response to papaverine, an agent partially dependent on endothelium, were unaltered. Indomethacin treatment did not correct the altered response to norepinephrine in mesenteric preparations studied in vivo in situ. Thus, the involvement of an EDCF which is sensitive to indomethacin blockade could be discarded. Since indomethacin treatment corrected the decreased response to acetylcholine observed in both mesenteric arterioles perfused in vitro or tested in vivo in situ, it is suggested that in arterioles of DOCA-salt hypertensive rats, an EDCF is involved in the decreased response to acetylcholine. Smooth muscle vasodilating capability appears to be unaltered.

Experimental chronic interstitial pancreatitis induced by scorpion toxin in rats.

Scorpion venom effects in the gastrointestinal system have been investigated both in men and experimental animals. Pancreatic flux and enzyme content are increased by TsTX, the purified venom from the scorpion Tityus serrulatus. In this study male rats received a single intravenous injection of TsTX. They were sacrificed 20 days later and their pancreas removed. Histopathological studies showed interstitial fibrosis, mononuclear infiltrate, acinar atrophy and ductal dilatation. There also appeared, although less frequently, eosinophil infiltrates, ductular hyperplasia and dense eosinophilic secretion in enlarged ducts. All lesions were multifocal. Islet hyperplasia and nesidioblastosis were also observed.

Comparison of the effect of endothelin on microvessels and macrovessels in Goldblatt II and deoxycorticosterone acetate-salt hypertensive rats.

The response to endothelin, a novel 21-amino acid peptide, is investigated in isolated aortas with and without endothelium and in mesenteric microvessels in vivo-in situ, in Goldblatt II (GII) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Median effective concentrations and maximal responses to endothelin did not differ in aortas with endothelium isolated from GII, DOCA-salt hypertensive, and control rats. After removal of the endothelium, the potentiation of the aorta responses to endothelin was of the same magnitude in hypertensive and control rats. A closed-circuit television system was used to observe the microvascular bed of the exteriorized mesentery of anesthetized GII, DOCA-salt hypertensive, and control rats. The time necessary to induce a vasoconstrictor response was determined after the topical application of endothelin. Vessel diameters at rest and after endothelin application were also estimated. At the microcirculatory level, a greater reactivity to endothelin was observed in both hypertensive rat groups, whereas higher sensitivity to endothelin was recorded in the GII hypertensive microvessel preparations alone. It is suggested that the increased response to endothelin observed in hypertensive rats might be due to abnormal sensitivity or reactivity of the microvessels of these rats reflecting an alteration of the contractile sequence possibly at the plasma membrane level, or due to both. Endothelial dysfunction at the microcirculatory level, however, cannot be dismissed.