The role of ecotype-environment interactions in intraspecific trophic niche partitioning subsequent to stocking.

Worldwide, stocking of fish represents a valuable tool for conservation and maintenance of species exploited by recreational fishing. Releases of hatchery-reared fish are more and more recognized to have numerous demographic, ecological, and genetic impacts on wild populations. However, consequences on intraspecific trophic relationships have rarely been investigated. In this study, we assessed the impacts of supplementation stocking and resulting introgressive hybridization on the trophic niches occupied by stocked, local, and hybrid lake trout (Salvelinus namaycush) within populations of piscivorous and planktivorous ecotypes stocked from a wild piscivorous source population. We compared trophic niches using stable isotope analysis (δ13 C and δ15 N) and trophic position among the three genetic origins. Putative genetic effects were tested with phenotype-genotype association of "life history" ecological traits (body size, growth rate, condition index, and trophic niche) and genotypes (RADseq SNP markers) using redundant discriminant analysis (RDA). Results showed that sympatry resulting from the stocking of contrasting ecotypes is a risk factor for niche partitioning. Planktivorous populations are more susceptible to niche partitioning, by competitive exclusion of the local fish from a littoral niche to an alternative pelagic/profundal niche. Observed niche partitioning is probably a manifestation of competitive interactions between ecotypes. Our results emphasize that ecotypic variation should be considered for more efficient management and conservation practices and in order to mitigate negative impact of supplementation stocking.

Investigating genomic and phenotypic parallelism between piscivorous and planktivorous lake trout (Salvelinus namaycush) ecotypes by means of RADseq and morphometrics analyses.

Repeated adaptive ecological diversification has commonly been reported in fish and has often been associated with trophic niche diversity. The main goal of this study was to investigate the extent of parallelism in the genomic and phenotypic divergence between piscivorous and planktivorous lake trout ecotypes from Laurentian Shield lakes, Canada. This was achieved by documenting the extent of morphological differentiation using geometric morphometrics and linear measurements as well as the pattern of genomic divergence by means of RADseq genotyping (3925 filtered SNPs) in 12 lakes. Our results indicate that the two ecotypes evolved distinct body shape and several linear measurements in parallel. Neutral genetic differentiation was pronounced between all isolated populations (Mean FST  = 0.433), indicating no or very limited migration and pronounced genetic drift. Significant genetic differentiation also suggested partial reproductive isolation between ecotypes in the two lakes where they are found in sympatry. Combining different outlier detection methods, we identified 48 SNPs putatively under divergent selection between ecotypes, among which 10 could be annotated and related to functions such as developmental processes and ionic regulation. Finally, our results indicate that parallel morphological divergence is accompanied by both parallel and nonparallel genomic divergence, which is associated with the use of different trophic niches between ecotypes. The results are also discussed in the context of management and conservation of this highly exploited species throughout northern North America.

Iron homeostasis in osteoporosis and its clinical implications.

Osteoporosis has until now been considered to be a disease associated with abnormal calcium metabolism. However, an increasing number of clinical observations strongly suggest the association of iron overload with bone diseases, particularly in osteoporosis in menopausal women. The recent identification of hepcidin sheds new light into the crucial role of iron homeostasis in bone metabolism. Decreasing iron overload in cell studies as well as in animal experiments has been shown to improve bone cell metabolism and growth in vitro and in vivo. In view of the significant iron overload found in the aging population, especially in females, the therapeutic potential of lowering iron overload for the treatment of osteoporosis is suggested.

Molecular diagnosis of HIV and relevant novel technologies in mutation analysis.

HIV infection is one of the major threats to human health due to the lack of relevant vaccine and drugs to cure AIDS. Its early diagnosis is thus important in controlling HIV transmission. Molecular diagnosis of HIV can be performed qualitatively and quantitatively. Currently, molecular diagnosis of HIV infection is only used as a complementary diagnosis although viral load test is used to monitor disease progression and responsiveness to antiviral therapy. To optimize HIV assays, a variety of technological advances, such as the introduction of dUTP/UNG system, real-time detection platform, and coupling of more than one enzyme in molecular identification, have been integrated into new methods. With the development of more reliable HIV assays in the future, the molecular diagnosis of HIV is expected to be accepted as one of the standards in determining whether there is a HIV infection in resource-rich laboratories, which will play a crucial role in reducing HIV transmission.

Lung is an important source of atrial natriuretic factor in experimental cardiomyopathy.

The regulation of water and electrolyte homeostasis is multifactorial and includes the heart and kidneys as important regulatory centers. Within the heart, a recently discovered hormone, atrial natriuretic factor (ANF), has been implicated in the maintenance of water and salt balance. Primarily found in mammalian atria, ANF has been detected in low amounts in several tissues, including lungs. A disorder of the ANF system has been demonstrated in genetically cardiomyopathic hamsters, a model for human congestive cardiomyopathy. Atrial ANF gene expression and storage are decreased during development of this disease, while paradoxically, circulating levels of ANF are increased. We have hypothesized that an extracardiac source may contribute to ANF production in these pathological conditions. In this paper we provide evidence that ANF synthesis is stimulated in the lungs of hamsters during development of cardiomyopathy as revealed by increased ANF mRNA and peptide levels. Furthermore, we show that ANF synthesized in lungs is secreted and has identical chromatographic and biological properties to circulating ANF. The increased production of ANF in lungs may be physiologically important in preventing pulmonary edema. Alternatively, during cardiac dysfunction, lungs may play a compensatory role by increasing their contribution to plasma ANF levels.

Renal permeability alteration precedes hypertension and involves bradykinin in the spontaneously hypertensive rat.

Vascular permeability disorders have been described in experimental models, as well as in human hypertension. We recently described the fact that vascular permeability to albumin is heterogeneous in the normal rat. In the present study, we examine the contents of Evans blue dye (EB) bound to albumin in selected organs of unanesthetized Wistar Kyoto (WKY) and in spontaneously hypertensive rats (SHR) at various stages of development of hypertension. EB was injected in the caudal vein of paired 4, 8, 12, and 16-wk-old WKY and SHR. Rats were killed 10 min after EB injection and extraction of the marker was measured in selected tissues. In additional 4 and 16-wk-old animals, bradykinin B1 and B2 receptor antagonists (BKA) were also injected with EB. Renal contents of EB bound to albumin were higher in the SHR than in the WKY: 196 +/- 9, 202 +/- 10, 182 +/- 7, and 196 +/- 9, compared with 158 +/- 8, 155 +/- 7, 138 +/- 7, and 118 +/- 6 micrograms/g dry tissue, in the 4, 8, 12, and 16-wk-old rats, respectively. In the 4-wk-old SHR and WKY, blood pressure values were normal and comparable, yet the alteration in EB permeability was already present in the SHR. Both BKA failed to alter the renal EB extravasation in the WKY, but the B2-BKA restored the renal permeability to control levels in the SHR. We conclude that a selective defect in the renal vascular permeability to EB developed in the SHR. Since this finding precedes hypertension and is corrected by a selective B2-BKA, it is suggested that bradykinin is involved at an early stage of the disease in the SHR.

Therapeutic potential of RNA interference against cellular targets of HIV infection.

RNA interference is not only very promising in identifying new targets for drug development, siRNA/shRNA themselves may be directly used as therapeutic agents. In inhibiting viral infections by RNA interference, both viral targets and cellular proteins have been evaluated. Most of the early studies in this field had chosen viral targets for RNA interference. However, recent efforts are mainly focusing on cellular proteins for RNA silencing due to the realization that a variety of viral responses substantially minimize siRNA effects. With the application of siRNA approaching, many new cellular targets relevant to HIV infection have been identified. The value of siRNA/shRNA in the treatment of AIDS is largely dependent on better understanding of the biology of HIV replication. Efforts in the identification of cellular processes with the employment of siRNA/shRNA have shed some new lights on our understanding of how HIV infection occurs. Furthermore, the relative specific effects and simplicity of design makes siRNA/shRNA themselves to be favorable drug leads.

The hemodynamic and metabolic profiles of Zucker diabetic fatty rats treated with a single molecule triple vasopeptidase inhibitor, CGS 35601.

CGS 35601 is a triple vasopeptidase inhibitor (VPI) of angiotensin converting enzyme (ACE), neutral endopeptidase (NEP), and endothelin (ET) converting enzyme-1 (ECE-1), with respective IC(50) values of 22, 2, and 55 nM. The aim of the present study was to establish the hemodynamic profile of Zucker diabetic fatty (Zdf)-Fatty rats, a high-fat diet gene-prone model developing spontaneous Type 2 diabetes (T2D) and the effects of CGS 35601. Male Zdf-Fatty (14 weeks, n = 17-23), Zdf-Lean (14 weeks, n = 8-10), and Wistar (14 weeks, n = 9-10) rats on distinct diets were implanted with a catheter in the left carotid and placed individually in a metabolic cage for 30 days. The hemodynamic profile and some metabolic biomarkers were assessed daily. After a 7-day stabilization period, the Zdf-Fatty rats were divided into two groups: Group 1, controls (n = 7-10) receiving vehicle-saline (250 microl/hr) and Group 2, (n = 10-13) receiving increasing doses of CGS 35601 (0.1, 1, and 5 mg/kg/day x 6 days each, intra-arterially) followed by a 5-day washout period. Mean arterial blood pressure (MABP) of young Zdf-Fatty rats was compared with age-matched Zdf-Lean and Wistar rats, which were found similar. MABP decreased by 5.9% (from baseline at 102 +/- 5 to 96 +/- 4 mmHg), 12.7% (to 89 +/- 6 mmHg) and 21.6% (to 80 +/- 4 mmHg), at 0.1, 1, and 5 mg/kg/day, respectively, in CGS 35601-treated Zdf-Fatty rats. Systolic and diastolic blood pressures were similarly reduced. The heart rate was not affected. Hyperglycemic status and insulin-resistance were not modulated by short-term treatment. CGS 35601 presented an excellent short-term safety profile. This novel molecule and class of VPI may be of interest for lowering vascular tone. Further long-term studies, once cardiovascular and renal complications have developed in this T2D rat model are warranted to define the efficacy of this class of VPI.

Triple VPI CGS 35601 reduces high blood pressure in low-renin, high-salt Dahl salt-sensitive rats.

We previously reported that CGS 35601, a potent triple inhibitor of angiotensin-converting enzyme, neutral endopeptidase, and endothelin-converting enzyme 1, completely normalized mean arterial blood pressure (MABP) in 36-week-old spontaneously hypertensive rats, a normal renin model. The aim of the present study was to determine the effects of this triple vasopeptidase inhibitor (VPI) on the hemodynamic profile of instrumented, conscious, and unrestrained Dahl salt-sensitive (DSS) rats, a gene-prone, high-salt diet-induced low-renin hypertension model. Male DSS rats (mean weight [+/-SEM], 385 +/- 10 g) were fed a normal diet (Group 1) or a high-salt diet (Groups 2 and 3; 8% NaCl in food) for 6 weeks and then instrumented with a carotid catheter and placed individually in metabolic cages for 30 days. The hemodynamic, hematological, and biochemical profiles were assessed daily. Dose-dependent treatment started after a 7-day stabilization period in Groups 1 and 2 (vehicle dosage, 250 microl/hr) and Group 3 (CGS 35601 dosages of 0.1, 1, and 5 mg/kg/day for 6 days per dose by means of constant intra-arterial infusion), followed by a 5-day washout period. Two additional groups included normotensive Wistar rats (Group 4) and DSS rats that received a double high-salt solid (8% NaCl) and liquid (1% NaCl) diet (Group 5). The MABP in rats receiving CGS 35601 decreased in a dose-dependent fashion toward the baseline level observed in DSS rats receiving a normal diet. The heart rate was unaffected. The hemodynamic profile returned to normal during the washout period. This novel triple VPI is a potent and effective antihypertensive agent with a safe short-term profile that may be of interest for treating hypertension and other cardiovascular diseases. Other hypertensive rat models are being tested.

Characterization of ATP-diphosphohydrolase activities in the intima and media of the bovine aorta: evidence for a regulatory role in platelet activation in vitro.

The inner layer of the aorta contains the enzyme ATP diphosphohydrolase (ATPDase: EC 3.6.1.5) which catalyzes the sequential phosphorolysis of ATP----ADP----AMP. Two zones of the inner layer, the intima and media, were separated and both were shown to contain ATPDase activity of similar specific activity (0.08 and 0.10 U/mg protein, respectively). However, the media exhibited about 100-times more enzyme activity than the intima. Both preparations were virtually identical with respect to pH optima (7.5), migration patterns after electrophoresis under non-denaturing conditions, relative rates of ATP and ADP hydrolysis and potency to inhibit ADP-induced platelet aggregation in both human platelet-rich plasma and whole blood. The IC50 values for ADP (2 microM)-induced aggregation were 6.8 and 12.9 mU/ml in platelet-rich plasma and whole blood, respectively. Addition of ATPDase to platelets pre-aggregated with ADP resulted in a dose-dependent disaggregation in platelet-rich plasma (IC50 4.9 mU/ml), but not in whole blood. When both ATPDase (5.6-58.7 mU/ml) and ATP (0.5-10 microM) were added to platelet-rich plasma, there was an immediate dose-dependent aggregation of platelets followed by a slowly developing disaggregation. These data show that ATPDase is present in both the intima and media layers of bovine aorta and suggest a dual role for this enzyme in platelet activation. By converting ATP released from damaged cells into ADP, the enzyme could facilitate platelet aggregation at the site of vascular injury, whereas the subsequent conversion of ADP to AMP could inhibit or reverse platelet aggregation. The consequence of these activities would be to control the growth of a platelet thrombus.

Profiling biochemical and hemodynamic markers using chronically instrumented, conscious and unrestrained rats undergoing severe, acute controlled hemorrhagic hypovolemic shock as an integrated in-vivo model system to assess new blood substitutes.

The aim of the present study was to assess several biochemical and physiological endpoint parameters alongside controlled hemorrhagic and recovery phases of chronically instrumented, conscious and unrestrained healthy rats. Male Sprague-Dawley rats (12-14 weeks; 430+/-20 g; n=22-18) were instrumented with a saline-perfused femoral arterial catheter and placed individually in a metabolic cage for up to 20 days, allowing instant assessments of the hemodynamic profile and blood and urine sampling for hematological profile and biochemical measurements to assess hepatic, renal and metabolic functions. In addition, body weight, food and water intake, and diuresis were monitored daily. After a 7-day stabilization period, the rats underwent severe and acute hemorrhagic shock (HS) (removal of 50% of total circulating blood volume), kept in hypovolemic shock for an ischemic period of 50 min and then resuscitated over 10 min. Gr. 1 was re-infused with autologous shed blood (AB; n=10) whereas Gr. 2 was infused 1:1 with a solution of sterile saline-albumin (SA; 7% w/v) (n=8-12). Ischemic rats recovered much more rapidly following AB re-infusion than those receiving SA. Normal hemodynamic and biochemical profiles were re-established after 24 h. Depressed blood pressure lasted 4-5 days in SA rats. The hematological profile in the SA resuscitated rats was even more drastically affected. Circulating plasma concentrations of hemoglobin (-40%), hematocrit (-50%), RBC (-40%) and platelets (-41%) counts were still severely decreased 24 h after the acute ischemic event whereas WBC counts increased 2.2-fold by day 4. It took 5-9 days for these profiles to normalize after ischemia-reperfusion with SA. Diuresis increased in both groups (by 45+/-7% on day 1) but presented distinct electrolytic profiles. Hepatic and renal functions were normal in AB rats whereas altered in SA rats. The present set of experiments enabled us to validate a model of HS in conscious rats and the use of an integrated in vivo platform as a valuable tool to characterize HS-induced stress and to test new classes of blood substitutes in real time, post-event, over days.

C-reactive protein inhibits intracellular calcium mobilization and superoxide production by guinea pig alveolar macrophages.

C-reactive protein (CRP) is a prototypical acute-phase reactant, the humoral and plasma concentrations of which rise dramatically after tissue injury or inflammation. The effects of CRP on superoxide production and intracellular calcium mobilization by guinea pig alveolar macrophages challenged with platelet-activating factor (PAF), N-formyl-methionyl-leucyl-phenylalanine (fMLP), and phorbol 12-myristate 13-acetate (PMA) were studied. CRP by itself did not activate alveolar macrophages up to a concentration of 100 micrograms/ml, whereas it inhibited superoxide production in a time- and dose-dependent manner with median inhibitory concentration (IC50) values of 4.2 +/- 0.3, 3.0 +/- 0.2, and 3.2 +/- 0.3 micrograms/ml for PAF (10(-7) M), fMLP (10(-7) M), and PMA (10(-9) M), respectively. When CRP was incubated with the agonists before addition to cells, it inhibited PMA-, PAF-, and to a lesser extent fMLP-induced superoxide production. CRP also attenuated the rise in intracellular free calcium levels evoked by fMLP or PAF in a dose-dependent manner. These findings suggest that CRP may play a role in attenuating tissue damage secondary to activation of alveolar macrophages by inhibiting superoxide generation and mobilization of intracellular free calcium.

Pulmonary surfactant lipids inhibit prostanoid production of guinea pig alveolar macrophages.

Changes in the amount and composition of pulmonary surfactant are important features of the adult respiratory distress syndrome. The goal of the present study was to investigate the effects of natural surfactant material and several of its lipid components on prostanoid production and superoxide generation by guinea pig alveolar macrophages. Natural surfactant (10-500 micrograms/ml) inhibited (up to 65%) prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) production elicited by platelet-activating factor (PAF, 10(-6) M) and arachidonic acid (5 x 10(-6) M) but not fMet-Leu-Phe (10(-7) M). Dioleyl-phosphatidylglycerol (diOPG, 1-100 micrograms/ml) and dioleyl-phosphatidylcholine (diOPC, 1-100 micrograms/ml) prevented fMet-Leu-Phe- and PAF-stimulated prostanoid release in a concentration-dependent fashion with a maximal inhibition of 94%. DiOPC (100 microgram/ml) also inhibited arachidonic acid induced PGE2 production by 67%. Phosphatidylcholine (100 micrograms/ml) and sphingomyelin (10-100 micrograms/ml) significantly attenuated TxB2 production elicited by arachidonic acid. Neither PAF- nor fMet-Leu-Phe-stimulated superoxide production was affected significantly by natural surfactant and its lipid components with the exception of phosphatidylcholine. At a concentration of 100 micrograms/ml, phosphatidylcholine decreased superoxide production by about 57% in response to PAF. These results show that diOPC and diOPG are capable of inhibiting prostanoid production of guinea pig alveolar macrophages in response to inflammatory stimuli and suggest that a decrease in the diOPG and diOPC content of surfactant would lead to enhanced intrapulmonary formation of prostanoids and consequently to the deterioration of pulmonary function in the adult respiratory distress syndrome.

Guinea pig lung eosinophil: purification and prostaglandin production.

Guinea pig lung eosinophils have been purified from bronchoalveolar lavage (BAL) fluid, and the production of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto-PGF1 alpha was measured after stimulation with phorbol myristate acetate (PMA), platelet-activating factor (PAF), and formyl-methionyl-leucyl-phenylalanine (fMLP). A combination of plating and discontinuous Percoll gradient centrifugation was used to purify eosinophils. The purity of eosinophils in fraction E (interface between Percoll density 1.057-1.068) was around 96%, and the viability was 99%, with a mean yield of 2.7 x 10(6) cells per guinea pig. Similarly, in fraction D (interface between Percoll density 1.047-1.057), the mean purity of eosinophils was 76% and the viability of cells was 99%, with a mean yield of 1.1 x 10(6) cells per guinea pig. Purified eosinophils produced TXB2 predominantly after stimulation with PMA, fMLP, and PAF. The 6-keto-PGF1 alpha was slightly increased in cell supernatants after stimulation with PMA and fMLP, but PGE2 was not elevated with any stimulus. The highly purified eosinophils of fraction E generated amounts of TXB2 and 6-keto-PGF1 alpha similar to the amount generated by eosinophils contaminated with some macrophages (fraction D). These results suggest a role for eosinophils in the production of TXA2 by guinea pig lung.

Atrial natriuretic factor immunoreactivity in human fetal lung tissue and perfusates.

Immunoreactive atrial natriuretic factor (ANF) was detected in human fetal homogenates and perfusates using a sensitive and specific radioimmunoassay for the 28 amino acid (C-terminal) fragment. Three peaks of ANF immunoreactive material were found in the lung homogenates. With high performance liquid chromatography, the elution characteristics of the first immunoreactive peak were the same as those of circulating human ANF. The other two peaks have not been characterized, although one had a position similar to the 126 amino acid rat prohormone (Asn 1-Ile 110-Tyr 126). The time course of release of immunoreactive ANF by perfused human fetal lungs was also studied. It is suggested that ANF may play a role in early pulmonary function.

ET(B) receptor and nitric oxide synthase blockade induce BQ-123-sensitive pressor effects in the rabbit.

Endothelin-1 (0.25 nmol/kg, injected into the left cardiac ventricle) induces a protracted increase of mean arterial pressure that is significantly reduced by the selective ET(A) receptor antagonist BQ-123 (1 and 10 mg/kg) in the anesthetized rabbit. The sole administration of the selective ET(B) antagonist BQ-788 (0.25 mg/kg) induces a pressor response abolished by BQ-123 (1 mg/kg). Concomitant to the increase in mean arterial pressure, BQ-788 induces a significant increase in plasma levels of endothelin-1 and its precursor big endothelin-1. The nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) also increases arterial blood pressure, and the response is reduced dose-dependently by BQ-123 (1 and 10 mg/kg). In addition, the administration of BQ-788 in the presence of L-NAME induced a further increase in arterial blood pressure. The duration of the pressor response to L-NAME is also significantly reduced by an endothelin-converting enzyme inhibitor, phosphoramidon (10 mg/kg). Finally, L-NAME induces an increase in plasma levels of big endothelin-1 but not endothelin-1. Our results illustrate that blockade of either nitric oxide synthase or ET(B) receptors triggers a raise in plasma levels of endothelin-1 or its precursor. These later moieties are suggested to be significantly involved, through the activation of ET(A) receptors, in the pressor effects of L-NAME and BQ-788 in the anesthetized rabbit.

Release of immunoreactive atrial natriuretic factor from the isolated perfused rat lung.

The secretion of ANF by the rat lung was demonstrated in the present study. Four forms of immunoreactive ANF were detected in rat lung homogenates, including the 126 amino acid prohormone but only a low molecular mass peptide was released during lung perfusion. The released ANF inhibited forskolin-stimulated aldosterone secretion from rat zona glomerulosa cell suspensions, and this biological effect was comparable to that of the synthetic C-terminal part of the prohormone (Arg-101-Tyr-126).

Effect of indapamide on phosphate metabolism and vascular reactivity.

The effect of indapamide, a nonthiazide diuretic, on urinary electrolytes, renal hemodynamics, and tissue inorganic phosphate was examined in normal anesthetized rats, as well as on vascular reactivity in vitro. Intravenous injections of 0.5 ml/kg of 1 x 10(-5), 1 x 10(-4), and 1 x 10(-3) M indapamide solutions reduced mean arterial pressure from 123 to 114, 130 to 113, and 128 to 114 mm Hg and the plasma phosphate concentrations from 6.4 to 4.2, 6.6 to 4.8, and 7.0 to 4.5 mg/dl, respectively. Similarly, there was a dose-dependent effect of indapamide on fractional excretion of phosphate, which increased from 17 to 44, 24 to 53, and 18 to 75 percent in animals receiving increasing doses of indapamide. This effect of indapamide on the external phosphate balance was associated with significant reduction of kidney cortex and skeletal muscle total inorganic phosphate. In contrast, fractional sodium excretion augmented by 2.6, 2.5, and 2.5 percent, respectively, at each dose of indapamide. This compound also reduced significantly the contractions of strips of rabbit aorta and mesenteric artery elicited by norepinephrine (0.01 to 1.0 micrograms/ml). These results suggest that indapamide-induced reduction of blood pressure could be mediated by an effect of this drug on phosphate balance, and probably on vascular reactivity.

Changes in vasoconstrictive hormones, natriuretic peptides, and left ventricular remodeling soon after anterior myocardial infarction.

OBJECTIVE: Our purpose was to study the changes in vasoconstrictive neurohormones, N-terminal proatrial natriuretic peptide (Nt-proANP), and brain natriuretic peptide (BNP) and their relationship with left ventricular (LV) remodeling soon after anterior myocardial infarction (MI). BACKGROUND: The Healing and Afterload Reducing Therapy (HEART) trial has shown that early use of ramipril improves left ventricular ejection fraction (LVEF) and attenuates LV remodeling when initiated soon after MI. This neurohumoral substudy of HEART investigates the changes in vasoconstrictive and natriuretic peptides and their relationship with LV remodeling. METHODS: One hundred twenty-two patients had blood drawn for the measurement of catecholamines, endothelin-I, angiotensin II, Nt-proANP and BNP, and prostacyclins within 24 hours of an MI, and at 3, 14, and 90 days after the MI. Quantitative echocardiograms were performed at baseline and at 14 days. RESULTS: All neurohormones except angiotensin II (P =.12) and prostaglandins were significantly elevated at baseline. Vasoconstrictive neurohormones decreased significantly over time but remained elevated at 14 days. Both Nt-proANP and BNP were elevated within the first 14 days. BNP decreased significantly by 90 days, whereas Nt-proANP exhibited no change between 14 and 90 days. Ramipril decreased plasma levels of angiotensin II at 3 days but had no effect on the other neurohormones. CONCLUSIONS: Neurohumoral activation occurs and persists in patients with anterior MI and overall preserved LV function. Ramipril had only a modest impact on neurohormones despite its significant benefits on LV remodeling soon after MI.

The rat isolated colon as a specific assay organ for angiotensin.

1. The antagonism of the contractile effects of prostaglandins F(2alpha) and E(2) by polyphloretin phosphate (PPP) was studied on the rat isolated colon.2. PPP (20 mug/ml) was found to reduce the myotropic action of angiotensin I (10 ng/ml) and II (0.3 ng/ml) whereas larger doses of both agents were not influenced.3. It is concluded that when a mixture of antagonists is used, including PPP, the rat isolated colon can be used to assay angiotensin with accuracy and specificity. The addition of 8-L-ala-AT(II) affords a further test of specificity.