bluuebunny/crossref_metadata_2025 huggingface dataset:
Watershed, reach, and riparian influences on stream fish assemblages in the Northern Lakes and Forest Ecoregion, U.S.A.
Authors: Wang Lizhu , Lyons John , Rasmussen Paul , Seelbach Paul , Simon Thomas , Wiley Michael , Kanehl Paul , Baker Ed , Niemela Scott , Stewart Paul M
Published: June 2003

We analyzed data from 79 watersheds in an undegraded U.S. ecoregion to identify key environmental factors that explained stream fish assemblage patterns and to evaluate the relative influence of environmental factors operating at different spatial scales. A few key factors from the watershed, reach, and riparian scale explained a significant amount of the variance in fish attributes. Three environmentfish associations were evident. Top carnivores and intolerant cold-water fishes were associated with relatively narrow, deep, high-gradient, cold streams with strong groundwater inputs. Tolerant cyprinids occurred in small streams with low groundwater input, low dissolved oxygen, and abundant macrophytes. A diverse assemblage (Cyprinidae, Catostomidae, Centrarchidae, Percidae) existed in warm, wide streams in watersheds dominated by lacustrine sand and gravel geology and abundant wetlands and lakes. Overall, reach-scale variables directly explained the most, watershed-scale variables less, and riparian-scale variables the least variation in fish attributes. Watershed and riparian variables had indirect connections with fishes through their direct influence on reach variables. In conjunction with findings from more degraded regions, we conclude that the relative influence of reach-scale variables on fishes are greatest in undegraded areas and that direct effects of watershed-scale variables are increasingly important as human modifications of the landscape increase.
The influence of prawn trawling on sessile benthic assemblages in Gulf St. Vincent, South Australia
Authors: Tanner Jason E
Published: June 2003

Most experimental studies on the effects of trawling on the benthos use remote sampling techniques and are conducted in recently trawled areas. Thus it is difficult to determine the effects of trawling on previously unfished areas, and the fates of individual animals cannot be followed. In this study, I follow the fates of individuals of several sessile taxa when exposed to experimental trawling in areas that have not been trawled for some 1520 years. Although there was a significant trawling by location effect for all multivariate analyses and most individual taxa, I found that trawling had an overall negative effect on the benthos. Epifauna at trawled sites decreased in abundance by 28% within 2 weeks of trawling and by another 8% in the following 23 months (compared with control sites). Seasonal seagrasses were also less likely to colonise trawled sites than untrawled sites. The persistence of most taxa declined significantly in trawled areas compared with untrawled areas. In contrast to this, the recruitment rates of several taxa into visible size classes increased after trawling, presumably because of a reduction in competition.
Density-dependent predation by brown bears (Ursus arctos) on sockeye salmon (Oncorhynchus nerka)
Authors: Quinn T P , Gende S M , Ruggerone G T , Rogers D E
Published: June 2003

The number of sockeye salmon (Oncorhynchus nerka) killed by brown bears (Ursus arctos) in 13 streams over more than a decade in southwestern Alaska was best explained by an asymptotic increase to about 3000 salmon killed per stream per year as salmon density increased to 10 000 fish·ha1of stream. Divergence from this pattern at some streams probably reflected variation in the number of bears using the stream (which we did not determine) and variation in salmon biomass consumed per fish killed. Daily surveys at one creek over 11 years revealed about 100130 salmon killed per day, ranging from a few to over 600. Higher proportions of the available salmon were killed early and late in the season, when densities were low. Thus the number of salmon killed within and among years increased with salmon abundance but at a declining rate, and the proportion killed generally decreased. Our previous work indicated that the average proportion of salmon killed among streams was controlled mostly by stream size, affecting the ability of bears to catch salmon. These findings are important for understanding the effects of bears on salmon population dynamics and their role in the transport of nutrients from salmon carcasses.
Effects of alternative control rules on the conflict between a fishery and a threatened sea lion (Phocarctos hookeri)
Authors: Breen Paul A , Hilborn Ray , Maunder Mark N , Kim Susan W
Published: June 2003

In New Zealand, a fishery for squid (Nototodarus sloanii) incidentally catches a threatened sea lion, Phocarctos hookeri. Bycatch is managed with an annual limit designed to ensure rebuilding of the sea lion population. We explore the conservation and cost effects of the current limit and two simple alternative rules, comparing them with no fishing and unrestricted fishing. We fitted an age-structured Bayesian model to sea lion pup estimates to obtain samples of the joint posterior distribution of parameters; from these we made 100-year simulations with five harvest control rules under six different sets of environmental conditions. The base-case fit suggests that the current sea lion population may be near its carrying capacity, although this may be sensitive to modelling choices. The fishery bycatch constitutes little risk to the sea lion population in the absence of catastrophes and generates small marginal risks when catastrophes are simulated. The current management rule does not minimise the marginal risk of extinction, is much more costly to the fishery than simple alternative rules, and incurs greatest cost when risk is smallest. The model appears to be a good tool for evaluating alternative management strategies against predefined objectives.
Multidecadal trends in North American Atlantic salmon (Salmo salar) stocks and climate trends relevant to juvenile survival
Authors: Friedland K D , Reddin D G , McMenemy J R , Drinkwater K F
Published: June 2003

Landings of North American Atlantic salmon (Salmo salar) over the past century show multidecadal patterns, which most recently characterize unprecedented declines in abundance. Stock size is compared with sea surface temperature (SST) data in the marine nurseries of post-smolt Atlantic salmon. A previously described correlation between stock abundance and winter SST conditions was again documented; however, of more relevance to the survival of salmon post-smolts, a correlation was also observed between abundance and spring SST in the Gulf of St. Lawrence. The relevance of the winter SST correlation was further investigated by considering winter conditions in the freshwater nurseries as a factor causing elevated overwintering mortality of pre-migrant parr. The salmon abundance time series was compared with air temperature and rainfall trends averaged over time and space. Air temperature and rainfall do not appear to be significant environmental variables in shaping salmon recruitment. The timing of smolt runs appears to be out of synchronization with ocean conditions in the post-smolt nursery areas. The relationship between marine and freshwater impacts may change with changing climate conditions. Persistent positive phase forcing in the North Atlantic Oscillation raises the concern that recent declines in Atlantic salmon are, in part, due to global climate change.
Comparative regional assessment of factors impacting freshwater fish biodiversity in Canada
Authors: Chu Cindy , Minns Charles K , Mandrak Nicholas E
Published: June 2003

This study presents a broad analysis of freshwater fish species biodiversity in relation to environmental and stress metrics throughout Canada. Species presenceabsence data were used to calculate richness and rarity indices by tertiary watershed. Richness is higher in the southern parts of Canada, whereas rarity is concentrated in a "ring of rarity" around the periphery of the country. Environmental and stress indices were developed for each watershed using readily available mapped information. The environmental index was estimated using growing degree-days above 5°C, elevation range (m) within the watershed, mean annual sunshine hours, and mean annual vapour pressure (kPa). The number of crop farms, forestry, waste management, and petroleum refining facilities, road density (km·1000 km2), dwelling density, and discharge sites (chimneys and laundry outlets) per 1000 km2 described the human stresses in each watershed. Conservation priority rankings were developed for the watersheds using an integrative index of the three indices. Watersheds in southern Ontario and British Columbia were ranked high because they contain the greatest biodiversity and the most stress. This study indicates how regional analyses can guide fisheries and watershed management.
Wildfire impacts on phytoplankton communities of three small lakes on the Boreal Plain, Alberta, Canada: a paleolimnological study
Authors: Charette T , Prepas E E
Published: June 2003

Quantification of sedimentary pigments with high performance liquid chromatography enabled the examination of changes in phytoplankton community indicators after wildfire in three lakes on the Boreal Plain with 50-year sediment chronologies. The response of phytoplankton indicators to wildfire was strongest in the shallow Lake B19, with post-fire increased concentrations of β-carotene (all phytoplankton), cyanobacterial pigments (echinenone, canthaxanthin), and lutein (chlorophytes) (p < 0.05). In the relatively deep headwater Lake B3, the indicator for all phytoplankton was not different after fire (p = 0.3), but important changes occurred in the phytoplankton community for 4 years after fire. The concentrations of cyanobacterial (echinenone, myxoxanthophyll) and diatoms + chrysophytes (fucoxanthin) indicators were higher and lower (p < 0.05), respectively, after fire. The relatively deep and non-headwater Lake B4 was little impacted by fire. An increase in cyanobacterial biomass after fire is most likely to occur in shallow headwater lakes on the Boreal Plain.
Dynamics and chemistry of dissolved organic carbon in Precambrian Shield catchments and an impounded wetland
Authors: Moore T R , Matos L , Roulet N T
Published: June 2003

We examined the sources, sinks, and fluxes of dissolved organic carbon (DOC) and its chemical fractions over a 4-year period in upland and wetland catchments in the Experimental Lakes Area, Ontario. In an upland catchment, the major sources of DOC were precipitation, vegetation, and soil organic matter, resulting in a summer (June to October) export of 2.1 g·m2. DOC concentrations in peat pore water ranged from 20 to 60 mg·L1and were related to hydrologic pathways. DOC export from catchments containing wetlands ranged from 0.8 to 5.7 g·m2and export from the peatland portion of the catchment was estimated to be 2830 g·m2. Flooding to a depth of 1.2 m in the peatland section of one catchment resulted in an increase in pore-water and pond DOC concentrations, attributed to the decomposition of plant tissues and peat. Because only 14% of the catchment was flooded, impoundment did not result in a significant increase in DOC export. Between 85 and 93% of DOC was contained in the acid fractions, with small amounts in the neutral fractions. Flooding increased the proportion of the hydrophilic neutral fraction in peat pore waters for 2 years after flooding.
The allometry of cannibalism in piscivorous fishes
Authors: Juanes Francis
Published: June 2003

Cannibalism is a widespread phenomenon that can have strong population and community effects. In this study, I compare the prey size  predator size relationships of diets with and without cannibalized prey for four piscivorous species and five populations that are commonly cannibalistic and where large databases exist. I then examine the resultant trophic niche breadths (range of relative prey size consumed) to quantify whether inclusion of cannibalized prey in the diet slows down the decline in trophic niche breadth that many large predators exhibit as they grow. When comparing diets including cannibalized prey with those without, consistent differences were found among all predator species. In all cases, the slope of the upper bound of the predator size  prey size scatters was larger for cannibal predators compared with noncannibals, suggesting selectivity for larger cannibal prey, which may be driven by higher rates of size-dependent capture success with familiar prey. The slopes of the upper bounds of the cannibal relative prey size vs. predator size scatter also tended to be larger than the upper-bound slopes for diets without conspecific prey. Finally, for all species, mean trophic breadth of diets including cannibalized prey were larger than those not including cannibal prey, suggesting that relatively large prey sizes may always be available for cannibals.
Spatial patterns in lotic invertebrate community composition: is substrate disturbance actually important?
Authors: Death Russell G
Published: June 2003

Twenty-five forest streams were sampled in August 1994 in Te Urewera National Park, New Zealand, to examine the effect of substrate disturbance on invertebrate community structure. Stream size, flow permanence, and riparian cover were more influential than substrate disturbance in affecting invertebrate composition. Three community types were distinguishable based on these three factors: small (<1 m wide), intermittent streams were dominated by Chironomidae; larger (1215 m wide), open streams were dominated by Chironomidae, Plecoptera, and Ephemeroptera; and intermediate-sized (110 m wide) streams with continuous riparian cover were dominated by mayflies and caddisflies. Periphyton biomass was negatively affected by substrate disturbance but not to the same degree as reported by others studying unshaded streams. This may explain why the influence of substrate disturbance on community composition was less than that of stream size, flow permanence, and riparian cover. The key effect of substrate disturbance on postdisturbance community composition in these light-limited New Zealand streams appears to be the removal of animals rather than food loss. Thus, differences between communities that experience high flows and those that do not are far less than they might be in unshaded streams in which the food base is more severely affected by substrate disturbance.
Endothelium and myocyte cellular insulin receptor alterations in a rat model of myocardial infarction
Authors: Jaroudi Wael A , Jurjus Abdo R , El-Sabban Marwan E , Kamal Maud T , Bitar Khalil M , Bikhazi Anwar B
Published: June 2003

Ischemic heart disease is considered to be one of the leading causes of death in adults. While extensive research on mechanisms contributing to the pathogenesis of myocardial infarction (MI) has been underway, it is not known whether insulin receptor characteristics and postreceptor signaling have been fully addressed as yet. Present work attempts to investigate whether the remodeling process effectively induces alteration(s) in insulin-binding characteristics at the coronary endothelium and cardiomyocytes using a rat heart model of MI. MI was induced by ligation of the left anterior descending coronary artery of adult male SpragueDawley rats. Two animal groups were used in the study: (i) sham-operated CHAPS-untreated and CHAPS-treated, and (ii) MI CHAPS-untreated and MI CHAPS-treated. A physical model describing 1:1 stoichiometry of reversible insulin binding to its receptors present on the endothelium and at cardiomyocytes after CHAPS treatment was considered for data analysis. Quantitation of the collected effluents after heart perfusion, the inlet at the aortic and outlet at the coronary sinus sites, were curve fitted using a first-order Bessel function, which determines the binding constants (kn), the reversible constant (kn), the dissociation constant (kd= kn/kn), and the residency time constant (τ = 1/kn). In addition, hearts were excised, separated into right and left ventricles, and individually weighed, and areas of infarcted regions were measured. Results of the MI group showed significant increases in relative heart mass, left ventricle mass, and right ventricle mass normalized to total body mass. MI induced severe ischemia and irreversible myocardial injury as assessed by planimetry and histologic studies. The data showed differences in insulin receptor affinities at the endothelial and cardiac myocytes in the sham and in the MI-operated rats. The observed reduction in the binding affinity of insulin at the myocyte postinfarction may explain the pathogenic role of insulin in ischemic heart disease and, hence, resistance. Therefore, insulin administration during and post MI might be cardioprotective.Key words: myocardial infarction, insulin binding, cardioprotection, insulin therapy.
Presence of neuropeptide Y and the Y1receptor in the plasma membrane and nuclear envelope of human endocardial endothelial cells: modulation of intracellular calcium
Authors: Jacques Danielle , Sader Sawsan , Perreault Claudine , Fournier Alain , Pelletier Georges , Beck-Sickinger Annette G , Descorbeth Magda
Published: June 2003

The aims of the present study were to investigate the presence and distribution of NPY and the Y1receptor in endocardial endothelial cells (EECs), to verify if EECs can release NPY, and to determine if the effect of NPY on intracellular calcium is mediated via the Y1receptor. Immunofluorescence, 3-D confocal microscopy and radioimmu noassay techniques were used on 20-week-old human fetal EECs. Our results showed that NPY and the Y1receptor are present in human EECs (hEECs) and that their distributions are similar, the fluorescence labelling being higher in the nucleus and more particularly at the level of the nuclear envelope when compared with the cytosol. Using radio immunoassay, we demonstrated that EECs are a source of NPY and can secrete this peptide upon a sustained increase of intracellular calcium ([Ca]i). Using fluo-3 and 3-D confocal microscopy technique, superfusion of hEECs as well as EECs isolated from rat adult hearts with increasing concentrations of NPY induced a dose-dependent, sustained increase in free cytosolic and nuclear Ca2+levels. This effect of NPY on EEC [Ca]iwas completely reversible upon washout of NPY and was partially blocked by BIBP3226, a selective Y1receptor antagonist. The results suggest that NPY and Y1receptors are present in the EECs of 20-week-old human fetal heart and they share the same distribution and localization inside the cell. In addition, EECs are able to secrete NPY in response to an increase in [Ca]i, and the Y1receptor as well as other NPY receptors seem to participate in mediating the effects of NPY on [Ca]iin these cells. Thus, NPY released by EECs may modulate excitationsecretion coupling of these cells.Key words: neuropeptide Y (NPY), nuclear envelope receptors, endocardial endothelial cells, NPY receptors, intracellular calcium.
Nucleoplasmic calcium regulation in rabbit aortic vascular smooth muscle cells
Authors: Abrenica Bernard , Pierce Grant N , Gilchrist James S.C
Published: June 2003

In this study, we investigated whether nucleoplasmic free Ca2+in aortic vascular smooth muscle cells (VSMCs) might be independently regulated from cytosolic free Ca2+. Understanding mechanisms and pathways responsible for this regulation is especially relevant given the role of a numerous intranuclear Ca2+-sensitive proteins in transcriptional regulation, apoptosis and cell division. The question of an independent regulatory mechanism remains largely unsettled because the previous use of intensitometric fluorophores (e.g., Fluo-3) has been criticized on technical grounds. To circumvent the potential problem of fluorescence artifact, we utilized confocal laser scanning microscopy to image intracellular Ca2+movements with the ratiometric fluorophore Indo-1. In cultured rabbit VSMCs, we found sarcoplasmic reticulum (SR) Ca2+ATPase (SERCA) pumps and ryanodine receptor (RyR) Ca2+channel proteins to be discretely arranged within a perinuclear locus, as determined by fluorescent staining patterns of BODIPY®FL thapsi gargin and BODIPY®FL-X Ry. When intracellular Ca2+stores were mobilized by addition of thapsigargin (5 μM) and activatory concentrations of ryanodine (1 μM), Indo-1 ratiometric signals were largely restricted to the nucleoplasm. Cytosolic signals, by comparison, were relatively small and even then its spatial distribution was largely perinuclear rather homogeneous. These observations indicate perinuclear RyR and SERCA proteins are intimately involved in regulating VSMC nucleoplasmic Ca2+concentrations. We also observed a similar pattern of largely nucleoplasmic Ca2+mobilization upon exposure of cells to the immunosuppressant drug FK506 (tacrolimus), which binds to the RyR-associated immunophillin-binding proteins FKBP12 and FKBP12.6. However, initial FK506-induced nucleoplasmic Ca2+mobilization was followed by marked reduction of Indo-1 signal intensity close to pretreatment levels. This suggested FK506 exerts both activatory and inhibitory effects upon RyR channels. The latter was reinforced by observed effects of FK506 to only reduce nucleoplasmic Indo-1 signal intensity when added following pretreatment with both activatory and inhibitory concentrations of ryanodine. These latter observations raise the possibility that VSMC nuclei represent an important sink of intracellular Ca2+and may help explain vasodilatory actions of FK506 observed by others.Key words: Ca2+, RyR, SERCA, cell nucleus, FK506, thapsigargin, ryanodine.
Angiotensin II AT1 receptor internalization, translocation and de novo synthesis modulate cytosolic and nuclear calcium in human vascular smooth muscle cells
Authors: Bkaily G , Sleiman S , Stephan J , Asselin C , Choufani S , Kamal M , Jacques D , Gobeil, Jr F , D'Orléans-Juste P
Published: June 2003

The present study was designed to verify if human (h) Angiotensin II (Ang II) type-1 receptor (hAT1R) undergoes internalization, nuclear translocation, and de novo synthesis in primary culture of human aortic vascular smooth muscle cells (hVSMCs) and if overexpression of this receptor modulates sustained free cytosolic ([Ca]c) and nuclear ([Ca]n) calcium. 3-dimensional (3-D) confocal microscopy was used to monitor free intracellular Ca2+ and hAT1R-green fluorescence protein (GFP) fusion protein in cultured hVSMCs. Immunofluorescence studies showed the presence of hAT1R and the absence of hAT2R in normal hVSMCs. Using 3-D imaging technique, hAT1 receptors were localized at the sarcolemma and in the cytosolic and nuclear compartments. In native as well as in normal hAT1R or hAT1R GFP overexpressing hVSMCs, Ang II (109 and 104 M) induced internalization and nuclear translocation of this type of receptor. The internalization of hAT1Rs is mediated via clathrin-coated pits and vesicles pathway. This phenomenon of trancellular trafficking of receptors was associated with an increase of hAT1R. The Ang II induced increase of hAT1R density was prevented by the protein synthesis inhibitor cycloheximide. Overexpression of hAT1R and hAT1RGFP decreased both basal cytosolic and nuclear Ca2+. In normal hVSMCs and low hAT1RGFP overexpressing hVSMCs, Ang II (1015 to 104 M) induced a dose-dependent sustained increase of [Ca]c and [Ca]n with an EC50 near 5 × 1011 and 5 × 109 M, respectively. Our results suggest that hAT1Rs are the predominant type of Ang II receptors in aortic hVSMCs and are present in the sarcolemma, the cytosolic and the nuclear compartments. Ang II rapidly induces hAT1R internalization, nuclear translocation, as well as nuclear de novo synthesis of this receptor. The hAT1R overexpression in hVSMCs modulates sustained [Ca]c and [Ca]n.Key words: angiotensin, calcium, protein synthesis, nucleus, AT1 receptor, nuclear de novo synthesis.
The endothelin system in pulmonary hypertension
Authors: Michel René P , Langleben David , Dupuis Jocelyn
Published: June 2003

Pulmonary hypertension (PH) may result from numerous clinical entities affecting the pulmonary circulation primarily or secondarily. It is recognized that vascular endothelial dysfunction contributes to the development and perpetuation of PH by creating an imbalance between vasodilating and antiproliferative forces and between vasoconstric tive and proliferative forces. In that context, endothelin-1 (ET-1) overproduction was rapidly targeted as a plausible contributor to the pathogenesis of PH. The lung is recognized as the major site for ET production and clearance. In all animal models of PH studied, circulating plasma ET-1 levels are elevated, accompanied by an increase in lung tissue expression of the peptide. The use of selective ETA and dual ETAETB receptor antagonists in these models both in prevention and in therapeutic studies have confirmed the contribution of ET-1 to the rise in pulmonary vascular tone, pulmonary medial hypertrophy, and right ventricular hypertrophy. This is found consistently in models affecting the pulmonary circulation primarily or producing PH secondarily. Recent clinical trials in patients with pulmonary arterial hypertension have confirmed the therapeutic effectiveness of ET-receptor antagonists in humans. We offer a systematic review of the pathogenic role of the ET system in the development of PH as well as the rationale behind the preclinical and ongoing clinical trials with this new class of agents.Key words: pulmonary circulation, pulmonary pathology, receptor, preclinical studies, clinical studies, antagonist.
Role of endothelin in human hypertension
Authors: Touyz Rhian M , Schiffrin Ernesto L
Published: June 2003

Endothelin-1 (ET-1) is a pleiotropic hormone produced primarily by the endothelium. Synthesis of ET-1 is stimulated by the major signals of cardiovascular stress, such as vasoactive agents (angiotensin II, norepinephrine, vasopressin, and bradykinin), cytokines (e.g., tumor necrosis factor α and transforming growth factor β), and other factors, including thrombin and mechanical stress. ET-1 induces vasoconstriction, is proinflammatory, promotes fibrosis, and has mitogenic potential, important factors in the regulation of vascular tone, arterial remodeling, and vascular injury. These effects are mediated via two receptor types, ETAand ETB. The role ET-1 plays in normal cardiovascular homeostasis and in mild essential hypertension in humans is unclear. However, certain groups of essential hypertensive patients may have ET-1-dependent hypertension, including blacks (subjects of African descent), salt-sensitive hypertensives, patients with low renin hypertension, and those with obesity and insulin resistance. ET-1 has also been implicated in severe hypertension, heart failure, atherosclerosis, and pulmonary hypertension. In all of these conditions, plasma immunoreactive ET levels are elevated and tissue ET-1 expression is increased. Accordingly, it is becoming increasingly apparent that ET-1 plays an important role in cardiovascular disease and in some forms of hypertension in humans. Data from clinical trials using combined ETAETBreceptor blockers have already demonstrated significant blood-pressure-lowering effects. Thus, targeting the endothelin system may have important therapeutic potential in the treatment of hypertension, particularly by contributing to the prevention of target organ damage and the management of cardiovascular disease.Key words: endothelin ETAand ETBreceptors, endothelium, vascular remodeling, essential hypertension.
Endothelin-1 in atherosclerosis and other vasculopathies
Authors: Bousette Nicolas , Giaid Adel
Published: June 2003

Atherosclerosis is a major risk factor for both myocardial infarction and stroke. A key aspect of this disease is the imbalance of vasoactive factors. In this concise review, we focus on the role of endothelin-1 in the atherosclerotic process and other vasculopathies. Previously, we have demonstrated that there is a correlation between the expression of endothelin and the underlying atherosclerotic lesion. Immunoreactivity was observed for both ET-1 and ECE-1 in endothelial cells, smooth muscle cells, and macrophages within lesions. Endothelin's role in atherosclerosis must extend from its varying physiological activities, including vasoconstriction, mitogenesis, neutrophil adhesion, and platelet aggregation, and hypertrophy, as well as its propensity to induce the formation of reactive oxygen species. We also discuss regulation of endothelin by angiotensin II, reactive oxygen species, thrombin, aging, and LDL in the cardiovascular system. Finally, we demonstrate the role of endothelin in pulmonary hypertension and transplant associated vasculopathy.Key words: ECE-1, receptors, human, vasoactive, mitogenic.
Role of endothelins in congestive heart failure
Authors: Moe Gordon W , Rouleau Jean L , Nguyen Quang T , Cernacek Peter , Stewart Duncan J
Published: June 2003

Despite major advances in conventional medical therapy, patients with heart failure continue to experience significant morbidity and mortality. Endothelin-1 (ET-1) is a potent vasocontrictor and mitogenic peptide that is activated in heart failure. There is increasing experimental and clinical evidence in support of an important role of ET-1 in the pathophysiology of heart failure. Manipulation of the activity of ET-1, especially using endothelin receptor blockers, has allowed for the further elucidation of the role of this neurohormonal system and development of novel therapeutic strategies in heart failure. Published clinical studies of these agents to date have involved relatively small numbers of patients with severe heart failure, followed for a relatively short period of time, and have mainly examined surrogate endpoints. Large-scale trials that address to hard clinical outcomes are ongoing and their results forthcoming. A key question that remains concerns whether selective ETA or dual ETAETB receptor blockade will be more effective.Key words: heart failure, endothelins, endothelin antagonists.
Endothelin-1 in chronic renal failure and hypertension
Authors: Larivière Richard , Lebel Marcel
Published: June 2003

Investigation into the role of endothelin-1 (ET-1) in renal function has revealed two major direct actions leading to the control of extracellular volume and blood pressure. These are the regulation of renal hemodynamics and glomerular filtration rate and the modulation of sodium and water excretion. In the rat remnant kidney model of chronic renal failure, ET-1 production is increased in blood vessels and renal tissues. These changes are related to an increase in preproET-1 expression and correlate with the rise in blood pressure, the development of cardiovascular hypertrophy, and the degree of renal insufficiency and injury. Selective ETAreceptor blockade prevents the progression of hypertension and the vascular and renal damage, supporting a role for ET-1 in chronic renal failure progression. The increase in ET-1 production can be associated with other local mediators, including angiotensin II, transforming growth factor-β1 and nitric oxide, the local production of which is also altered in chronic renal failure. In human patients with essential hypertension, atherosclerosis, and nephrosclerosis, plasma ET-1 levels are increased compared with patients with uncomplicated essential hypertension. Similarly, plasma ET-1 concentrations are markedly increased in patients with end-stage renal disease undergoing dialysis, and this correlates with blood pressure, suggesting that ET-1 may contribute to hypertension in these patients. The treatment of anemia in patients with renal failure with human recombinant erythropoietin increases blood pressure by accentuating the underlying endothelial dysfunction and the elevated vascular ET-1 production. Overall, these results support a role for ET-1 in hypertension and the end-organ damage associated with chronic renal failure. ETAreceptor blockade may then represent a potential target for the management of hypertension and cardiovascular and renal protection.Key words: endothelin-1, angiotensin II, nitric oxide, erythropoietin, chronic renal failure, hypertension, endothelium.
Endothelin in the perinatal circulation
Authors: Perreault Thérèse , Coceani Flavio
Published: June 2003

During the fetal period, blood is oxygenated through the placenta, and most of the cardiac output bypasses the lung through the ductus arteriosus. At birth, pulmonary vascular resistance falls with the initiation of ventilation. Coincidentally, the ductus arteriosus constricts. Endothelin-1 (ET-1) appears to play an important role during that transition period and postnatally. ET-1 can dramatically increase resistance in the placental microcirculation and may be involved in blood flow redistribution with hypoxia. At birth, the increase in oxygen tension is important in triggering ductus vasoconstriction. It is proposed that oxygen triggers closure of the ductus arteriosus by activating a specific, cytochrome P450-linked reaction, which in turn stimulates the synthesis of ET-1. On the neonatal heart, ET-1 has a positive chronotropic but negative inotropic effect. In the newborn piglet and the fetal lamb, both term and preterm, ET-1 causes a potent, long-lasting pulmonary vasoconstriction. Furthermore, a transient dilator response has been identified, and it is ascribed to nitric oxide formation. ET receptors are abundant in the piglet pulmonary vasculature. They are predominantly of the ETAconstrictor subtype, though ETB2constrictor receptors may also be present in certain species. The dilator response is linked to the ETB1receptor, and the number of ETB1receptors is reduced in hypoxia-induced pulmonary hypertension. ET-1 appears to be a causative agent in the pathogenesis of hypoxia- and hyperoxia-induced pulmonary hypertension as demonstrated by reversal of hemodynamic and morphological changes with treatment with an ETAreceptor antagonist. Findings are amenable to practical applications in the management of infants with pulmonary hypertension or requiring persistent patency of the ductus arteriosus.Key words: ductus arteriosus, neonatal pulmonary circulation, neonatal pulmonary hypertension, neonatal cardiomyocytes, fetus.
Role of ET-1 in the regulation of coronary circulation
Authors: Lavallée Michel , Thorin Eric
Published: June 2003

Given that circulating ET levels in heart failure, in particular, may reach physiological threshold for coronary constrictor responses, the primary objective of the present review is to consider coronary vessels as an important target for circulating and locally produced endothelin(s). In healthy vessels, ET-1 causes biphasic coronary responses characterized by a transient dilation of large and small arteries followed by a sustained constriction. ETBreceptors are pivotal in the early dilation of resistance vessels, whereas dilation of conductance vessels may be a secondary phenomenon triggered by flow increases. Exogenous ET-1 causes coronary constriction almost exclusively through ETAreceptor activation. Human and canine large epicardial coronary vessels display significant baseline ET-1 dependent tone in vitro and in vivo, an ETA-dependent process. In contrast, ETBreceptors located on smooth muscle cells are apparently less important for producing constrictor responses. NO production may serve as an important counter-regulatory mechanism to limit ET-dependent effects on coronary vessels. Conversely, in a dysfunctional endothelium, the loss of NO may augment ET-1 production and activity. By lifting the ET-dependent burden from coronary vessels, ET receptor blockade should help to ensure a closer match between cardiac metabolic demand and coronary perfusion.Key words: endothelin, ET receptors, coronary vessels, coronary blood flow, nitric oxide, shear stress, atherosclerosis, humans, animals.
Role of endothelins in animal models of hypertension: focus on cardiovascular protection
Authors: Moreau Pierre , Schiffrin Ernesto L
Published: June 2003

Investigation of the regulation of vascular function by endothelium-derived factors has been a prominent topic of research in the field of hypertension during the last decade. Of the different endothelial factors, endothelins, which play an important role in vasodilatationvasoconstriction balance, have been the subject of great interest and an impressive number of publications. This peptide, a very potent vasoconstrictor, triggers as well events involved in growth, proliferation, matrix production and local inflammation. In parallel, its role in hypertension has evolved from a simple vasoconstrictor to a central local regulator of vascular homeostasis contributing not only to the elevation of blood pressure, but also to the complications of hypertension. This review summarizes research on endothelins and its receptor antagonists in experimental hypertension, with special emphasis on vascular remodeling and target-organ protection.Key words: endothelin, endothelin antagonists, hypertension, vascular remodeling, hypertrophy, target-organ damage.
Role of endothelin in regulation of resistance, fluid-exchange, and capacitance functions of the systemic circulation
Authors: McNeill J Robert
Published: June 2003

This article reviews data at the in vivo whole animal and human level. The importance of both flow and pressure recordings and of the methods used to record these variables is emphasized. Exogenous administration of endothelin-1 evokes a transient depressor response mediated by endothelial endothelinBreceptors, but the predominate effect of endothelin-1 is a sustained increase in blood pressure resulting from increases in total peripheral resistance. Resistance in the superior mesenteric, renal, and hindquarter vascular beds of animals and forearm resistance in humans is increased. Both endothelinAand, to a lesser extent, endothelinBreceptors on vascular smooth muscle mediate the increases in resistance. Endothelin-1 evokes decreases in the precapillary/postcapillary resistance ratio, resulting in increased capillary pressure and net transcapillary filtration. Endothelin-1 evokes increases in mean circulatory filling pressure in animals and in constriction of the human dorsal hand vein. This venoconstrictor activity is mediated primarily through endothelinAand to a lesser extent endothelinBreceptors. Endogenously generated endothelin contributes to the hemodynamic effects of angiotensin and vasopressin in certain animal models of hypertension. Antagonists of endothelin evoke modest hemodynamic changes in healthy humans and in some healthy animals, and they decrease vascular resistance dramatically in several salt-sensitive rat models of hypertension and also in some hypertensive human subjects. Thus, endogenously generated ET appears to play a modest role in the healthy organism, but it likely plays a major role in many pathophysiological states as described in companion articles in this issue.Key words: hemodynamics, resistance, fluid exchange, capacitance, endothelin.
Modulation and roles of the endothelins in the pathophysiology of pulmonary embolism
Authors: Battistini Bruno
Published: June 2003

Recent research on the endothelins (ETs) and their pathways in acute pulmonary embolism (APE) has led to significant advances in the understanding of this disease. ETs are potent vasoconstrictors and bronchoconstrictors found abundantly in the lung and can be released by stimuli such as endothelial injury, hypoxia, or thrombin, a key product in the coagulation cascade. Many studies using different approaches and methods of inducing pulmonary embolization, both in vitro and in vivo in various species, have mostly shown that ETs play an important role in the pathophysiology of APE. These results were obtained by comparing the hemodynamic data in the presence or absence of various ETs inhibitors, but also by assessing the modulation of the ET-related elements of this system by molecular, cell biology, and pharmacological methods. Based on the current understanding, a mechanism involving the ET pathway in the pathophysiology of APE is proposed for the reader's considerations. We postulate that ETs are primary mediators in APE based on the following: (i) their source from pulmonary endothelial cells where the primary injury takes place; (ii) their direct vasconstrictive, bronchoconstrictive, and promitogenic effects via distinct ET receptors; and (iii) their indirect effects associated with the secondary release of thromboxane and other mediators, which are released from inflammatory cells and platelets, which together can potentiate the overall hemodynamic response, most specifically the pulmonary vascular bed. Such combined effects of ETs on bronchomotor and vasomotor tone in the lung can adversely affect ventilation perfusion matching and lead to severe hypoxemia without causing significant changes in the chest X-ray of these patients. Thus, we may consider ET inhibitors as future current therapeutic agents in patients with PE.Key words: pulmonary embolism, thrombus, air, pulmonary hypertension, blood gas, hypoxia, endothelin, endothelin receptor, antagonists.
Activation of sarcolemma and nuclear membranes ET-1 receptors regulates transcellular calcium levels in heart and vascular smooth muscle cells
Authors: Bkaily Ghassan , Choufani Sanaa , Sader Sawsan , Jacques Danielle , d'Orléans-Juste Pedro , Nader Moni , Kurban Ghada , Kamal Maud
Published: June 2003

The use of an ET-1 fluorescent probe in human heart and vascular smooth muscle cells showed that ET-1 receptors are present at both the sarcolemma and nuclear envelope membranes. The use of immunofluorescence studies showed that the ETA receptor was mainly present at the sarcolemma and cytosolic levels. However, the ETB receptor was present at the sarcolemma and the cytosol, as well as the nuclear envelope membranes and the nucleoplasm. In addition, ET-1 immunoreactivity was seen in the cytosol and the nucleus. Using Ca2+fluorescent probes such as Fluo-3, Indo 1, and yellow cameleon, as well as confocal microscopy three-dimensional image measurement technique, stimulation of ET-1 receptors at the sarcolemma membranes induced an increase of cytosolic and nuclear free Ca2+ levels. This effect of extracellular ET-1 was blocked by removal of extracellular calcium. Direct stimulation of ET-1 receptors at the nuclear envelope membranes also induced an increase of intranuclear free Ca2+ level. Our results suggest that the stimulation of sarcolemmal Ca2+ influx by ET-1 seems to be due to the activation of ETA and ETB receptors. However, the increase of nucleoplasmic Ca2+ levels by cytosolic ET-1 seems to be mediated via the activation of ETB receptors. Activation of nuclear membranes ETB receptors seems to prevent nuclear Ca2+ overload and may protect the cell from apoptosis.Key words: endothelin-1, endothelin-1 receptors, calcium, nuclear receptors, confocal microscopy.
Mechanisms and consequences of large artery rigidity
Authors: Et-Taouil Karima , Safar Michel , Plante Gérard E
Published: June 2003

In this review paper, the classical and more recently described mechanisms responsible for the structural and functional characteristics of large artery rigidity are described. Mostly important, these characteristics appear to be nonspecific to the primary disease process involved in arterial hypertension, diabetes mellitus, dyslipidemia, congestive heart failure, chronic uremia, and perhaps senescence, including vascular dementia. Nonspecific in terms of aetiology, the vasculopathy encountered in these diseases exhibits common structural and functional abnormalities. The identification of such abnormalities could well become the target of potent nonpharmacological and (or) pharmacological interventions capable of preventing or retarding morbidity and mortality. The structural characteristics responsible for large artery rigidity include smooth muscle cell hypertrophy, matrix collagen deposition, and recently described, dysfunction in proteoglycan metabolism. Functional abnormalities, such as bradykinin-dependent hyper-reactivity of smooth muscle cells and vasa vasorum microcirculation network disturbances, also appear to alter aortic wall rigidity. The physiopathology of target organ damage is then revisited, based on endothelial dysfunction, documented in large and resistance arteries, as well as in microcirculation networks, where altered permeability to macromolecules leads to interstitial matrix disorganization and cell damage. The clinical evaluation of large artery rigidity is described, and one of the noninvasive methods, evaluation of pulse-wave velocity, is validated in normal conditions and in disease processes. Finally, nonpharmacological and pharmacological therapeutic measures are presented, and includes physical exercise to reduce insulin resistance, and reninangiotensin-IIaldosterone modulators.Key words: large artery compliance, aortic structure, collagen, elastin, proteoglycans, vascular smooth muscle cells, vasa vasorum, target organ damage, pulse wave velocity, vascular pharmacology.
Hormonally derived sex pheromones in fish: exogenous cues and signals from gonad to brain
Authors: Stacey Norm , Chojnacki Andrew , Narayanan Annapurni , Cole Todd , Murphy Cheryl
Published: June 2003

Living in a medium that can limit visual information but readily exposes the olfactory organ to hormonal compounds released by conspecifics, fish throughout their long evolutionary history have had both clear cause and ample opportunity to evolve olfactory responsiveness to these potentially important chemical cues (hormonal pheromones). Indeed, water-borne steroids, prostaglandins, and their metabolites are detected with great sensitivity and specificity by the olfactory organs of diverse fishes, and exert important effects on reproductive behavior and physiology in major taxa including carps (goldfish), catfishes, salmon, and gobies. Best understood are goldfish, where periovulatory females sequentially release a preovulatory steroid pheromone and a postovulatory prostaglandin pheromone that dramatically affect male behavior, physiology, and reproductive fitness. Although the diverse array of hormonal products released and detected by fish indicates clear potential for species-specific hormonal pheromones, olfactory recordings showing similar patterns of hormone detection among closely related species provide little evidence of selection for specificity. By demonstrating that the actions of sex hormones and related products are not limited to reproductive synchrony within the individual, the relatively recent discovery of hormonal pheromones has considerably expanded our understanding of fish reproductive function, while providing valuable model systems for future study of olfactory function and pheromone evolution.Key words: pheromone, olfaction, 17α,20β-dihydroxy-4-pregnen-3-one, prostaglandin, sperm competition.
A neuroendocrine model for prolactin as the key mediator of seasonal breeding in birds under long- and short-day photoperiods
Authors: Sharp Peter J , Blache Dominique
Published: June 2003

Seasonal breeding is associated with sequential increases in plasma luteinizing hormone (LH) and prolactin in the short-day breeding emu, and in long-day breeding birds that terminate breeding by the development of reproductive photorefractoriness. A model of the avian neuroendocrine photoperiodic reproductive response is proposed, incorporating a role for prolactin, to account for neuroendocrine mechanisms controlling both long- and short-day breeding. The breeding season terminates after circulating concentrations of prolactin increase above a critical threshold to depress gonadotropin releasing hormone (GnRH) neuronal and gonadotrope (LH) activity. Subsequently, photorefractoriness develops for prolactin secretion and for LH secretion, independently of high plasma prolactin. The breeding season in the emu is advanced compared with long-day breeders, because after photorefractiness for both LH and prolactin secretion is dissipated, plasma concentrations of both hormones increase to maximum values while days are still short.Key words: seasonal breeding, prolactin, gonadotropin releasing hormone, photorefactoriness.