Pathogenesis of ascites in broilers raised at low altitude: aetiological considerations based on echocardiographic findings

This study reports novel insight into the aetiology of pulmonary hypertension and ascites in broiler chickens. The scope of measurements was focused on anatomical and functional parameters, and blood flow patterns in leghorns (resistant to ascites), fast-growing broilers (susceptible to ascites), broilers developing ascites, and ascitic broilers evaluated in vivo using echocardiography, and further examined in the context of postmortem findings. Both, in vivo observed features and postmortem findings, showed clear differences between broilers and leghorns, and between normal and ascitic broilers. Abnormalities in the heart chamber geometry and blood flow patterns were detected upon echocardiographic examination in all ascitic broilers. Right and left atrio-ventricular (AV) valve regurgitation were common findings in ascitic broilers and some apparently normal broilers, with left AV valve insufficiency being a predominant feature with respect to degree and frequency of occurrence. Blood flow disturbances were not detected in leghorns. Left ventricular fractional shortening (functional parameter) was considerably reduced (P < 0.01) in ascitic birds (mean: 21.7 +/- 2.0 SE) in comparison with normal broilers (mean: 39.1 +/- 3.6 SE), or leghorns (mean: 43.3 +/- 2.4 SE). The presented findings indicate that pathological and functional changes in the left ventricle and atrium play a significant role in the pathogenesis of ascites in broilers. Severe dilation of the left atrium and pulmonary veins seen on postmortem examination, as well as regurgitant blood flow in the left atrium, demonstrated by Doppler study in ascitic birds, provide evidence that chronically elevated pressure in the left atrium is involved in the aetiology of pulmonary hypertension and ascites in fast-growing broilers.     

日粮中添加L—NAME对肉鸡腹水综合征发生的影响及其机理

应用低温环境和日粮中添加三碘甲腺原氨酸（3，3，5－triiodothyronine,T3)诱发肉鸡腹水综合征，同时通过日粮添加一氧化氮合酶抑制剂L－NAME，研究了抑制NO的合成对肉鸡肺动脉压及肉鸡腹水综合征发生的影响。180羽AA肉鸡随机等分为对照组（C）、试验组（A、B），参试鸡14日前按常规条件饲养。14日龄后C组鸡按常规条件饲养，A、B组鸡舍温按每日1－2℃逐步降至12℃，同时日粮中添加T3 1．5mg/kg以诱发腹水综合征。另外，B组肉鸡从14日龄起在日粮中添加100mg/kgL－NAME至试验结束。分别于3、4、5、6周龄测定各组肉鸡肺动脉平均压（mean pulmonary arterial pressure,mPAP)、红细胞压积、右心全心比、血浆一氧化氮（NO）和内皮素（endothelin-1,ET-1)水平并记录腹水综合征发病率。结果显示：低温添加T3处理后，A、B组肉鸡腹水综合征发病率增加，但B组高于A组；A、B组肉鸡mPAP从5周龄起高于C组（P＜0．05）；A、B组右心全心比的升高分别在6、5周龄时出现，B组右心全心比的升高比A组提前1周；B组 肉鸡血浆NO水平低于A组，差异不显著；A、B组肉鸡血浆ET－1水平高于C组（P＜0．05）；在6周龄时，A组肉鸡心率明显降低，B组肉鸡心率明显升高。随着肺动脉高压和右心肥大的出现，心率的升高可能促进了右心衰竭和肉鸡腹水综合征的发生。上述结果提示，抑制NO的合成可能促进了肉鸡肺动脉高压，右心肥大的形成和肉鸡腹水综合征的发生。     

Calcium antagonists,diltiazem and nifedipine,protect broilers against low temperature‐induced pulmonary hypertension and pulmonary vascular remodeling

This study was designed to determine whether calcium antagonists, diltiazem and nifedipine, can depress low temperature‐induced pulmonary hypertension (PH) in broilers (also known as ascites) and to characterize their efficacy on hemodynamics and pulmonary artery function. Chicks were randomly allocated into six experimental groups and orally administered with vehicle, 5.0 mg/kg body weight (BW)/12 h nifedipine or 15.0 mg/kg BW/12 h diltiazem from 16 to 43 days of age under low temperature. The mean pulmonary arterial pressure (mPAP), the ascites heart index (AHI), the erythrocyte packed cell volume (PCV) and the relative percentage of medial pulmonary artery thickness were examined on days 29, 36 and 43. The data showed that administration of diltiazem protected broilers from low temperature‐induced pulmonary hypertension and vascular remodeling. Although nifedipine prevented mPAP from increasing during the early stage, it did not suppress the development of PH during the late stage and did not keep heart rate (HR), PCV, AHI and the thickness of pulmonary small artery smooth muscle layer at the normal levels. Taken together, our results showed that diltiazem can effectively prevent low temperature‐induced pulmonary hypertension in broilers with fewer side‐effects and may be a potential compound for the prevention of this disease in poultry industry.     

The effect of dietary chloride and bicarbonate on blood pH, haematological variables, pulmonary hypertension and ascites in broiler chickens.

1. The effect of supplementing grower diets with bicarbonate or chloride on haematological variables, pulmonary hypertension syndrome and ascites in broilers exposed to cold temperature was investigated. 2. High concentrations of dietary chloride had no effect on the pH of the venous blood but a low chloride/high bicarbonate diet significantly increased blood pH. There was no consistent effect of dietary chloride or bicarbonate concentrations on growth performance, although in 1 experiment birds given a low chloride/high bicarbonate diet consumed less food and gained less weight than controls. 3. Birds fed on high-chloride diets tended to have a higher incidence of ascites and pulmonary hypertension than controls. Birds fed on low-chloride and high-bicarbonate diets had significantly lower pulmonary hypertension and lower heart weights, which may have indicated a decrease in pulmonary and systemic blood pressure. 4. We conclude that increasing dietary bicarbonate and reducing dietary chloride has potential as a low cost and effective method to reduce the pulmonary hypertension which leads to ascites in broiler chickens.     

Nutritional approaches to ameliorate pulmonary hypertension in broiler chickens

This article reviews recent nutritional approaches for counteracting the development of pulmonary hypertension syndrome (PHS; ascites) in broiler chickens especially when they are reared at high altitudes. High altitudes impose the sustained stress of hypobaric hypoxia, which reduces the availability of atmospheric oxygen to red blood cells passing through the lungs, thereby causing systemic arterial hypoxaemia (undersaturation of haemoglobin with oxygen), pulmonary arterial hypertension and PHS/ascites in susceptible broilers. Proper nutritional strategies are needed to reduce metabolic activity and prevent the development of ascites especially when modern broilers are reared in regions where the existing altitudes limit the availability of atmospheric oxygen. This article also addresses controversies with regard to broiler nutrition in relation to PHS. For example, the catabolism of protein from feed ingredients incurs increased oxygen consumption, suggesting that feeding reduced‐protein diets to broiler chickens may result in reduced PHS incidences. However, experimental and field data indicate that feeding reduced‐protein diets to broilers subjected to hypobaric hypoxia increases the development of PHS. Controversies on the nutrition of unsaturated fat in relation to PHS are also discussed. In conclusion, hypoxia, acidosis, vasoconstriction and enhanced metabolic rate are triggers of PHS. Feeding reduced‐protein diets might promote the susceptibility of broilers to PHS by decreased dietary intake of arginine, decreased uric acid production and increased lipogenesis. Feeding high‐protein diets, dietary arginine supplementation, partial substitution of sodium bicarbonate for sodium chloride, feeding low‐fat diets and effective feed restriction programmes can be considered as nutritional approaches to prevent PHS.     

Ultrastructural and molecular changes in the left and right ventricular myocardium associated with ascites syndrome in broiler chickens raised at low altitude

The present study examines ultrastructural and molecular changes in ventricular myocardium associated with ascites cases in fast-growing broilers raised at low altitude. Extensive ultrastructural lesions were seen in the left and right ventricular myocardium of broilers with fulminant heart failure and ascites. Significant changes included lesions in the myofibril contractile apparatus, altered mitochondria, marked reduction in the myofibril component, and changes in the extracellular matrix (ECM) architecture. No lesions were observed in hearts of slow growing broilers, but mild to moderate changes (predominantly in the left ventriculum) were apparent in the hearts from some clinically normal, fast-growing broilers. SDS-PAGE profiles of washed myofibrils showed several distinctly different bands in preparations from left ventricular myocardium of ascitic birds. Western blot analysis of these samples revealed several fragments of myosin heavy chain, M-protein, and titin. Based on gelatinolytic activity, matrix metalloproteinases (MMP) in the cytosolic fraction of ventricular myocardium homogenates were identified as MMP-2. The relative activity of this enzyme appears to be considerably higher in preparations from broilers, particularly in the preparations from the left ventriculum of fast-growing broilers, in comparison to leghorns or slow growing broilers. The nature and distribution of the changes in the heart indicate that chronic cardiomyopathic process in the left ventricular myocardium occurs during the development of ascites. It is postulated that progressive deterioration of the left heart pump function caused by initial lesions in the left ventricular myocardium is a significant factor in the development of pulmonary hypertension and the pathogenesis of ascites in broilers raised at low altitude.     

Increased calcium deposits and decreased Ca-ATPase in erythrocytes of ascitic broiler chickens

The decrease of erythrocyte deformability may be one of the predisposing factors for pulmonary hypertension and ascites in broiler chickens. In mammals, the cytoplasmic calcium is a major regulator of erythrocyte deformability. In this study, the erythrocyte deformability was measured, and the precise locations of Ca²⁺ and Ca²⁺-ATPase in the erythrocytes were investigated in chickens with ascites syndrome induced by low ambient temperature. The results showed that ascitic broilers had higher filtration index of erythrocyte compared with control groups, indicating a decrease in erythrocyte deformability in ascitic broilers. The more calcium deposits were observed in the erythrocytes of ascitic broilers compared with those of the age-matched control birds. The Ca²⁺-ATPase reactive grains were significantly decreased on the erythrocyte membranes of ascitic broilers. Our data suggest that accumulation of intracellular calcium and inhibition of Ca²⁺-ATPase might be important factors for the reduced deformability of the erythrocytes of ascitic broilers.     

Right ventricular failure and ascites in broiler chickens caused by phosphorus-deficient diets

Phosphorus-deficient diets fed to broiler chicks from day 1 to day 21 induced rickets. Some chicks were stunted, but most grew well, though they had increased respiratory rates, high arterial carbon dioxide partial pressure, and low oxygen partial pressure and were polycythemic. Most of the broilers that died showed signs of pulmocardiovascular abnormalities, some died from hypoxia, and some died from right ventricular failure with or without ascites. Many broilers had mild to marked right ventricular hypertrophy and dilation with or without ascites when examined at 21 days. It is suggested that right ventricular hypertrophy and dilation was a response to pulmonary arterial hypertension caused by chronic hypoxia, which resulted from inability to breathe normally because of poor rib strength and infolding. When right ventricular failure occurred, it was secondary to right ventricular hypertrophy and dilation.     

Effects of early feed restriction and cold temperature on lipid peroxidation, pulmonary vascular remodelling and ascites morbidity in broilers under normal and cold temperature

Two experiments were conducted to evaluate the effects of early feed restriction on lipid peroxidation, pulmonary vascular remodelling and ascites incidence in broilers under normal and low ambient temperature. In experiment 1, the restricted birds were fed 8h per day either from 7 to 14 d or from 7 to 21 d, while the controlled birds were fed ad libitum. In experiment 2, the restricted birds were fed 80 or 60% of the previous 24-h feed consumption of full-fed controls for 7 d from 7 to 14 d. On d 14, half of the birds in each treatment both in experiment 1 and experiment 2 were exposed to low ambient temperature to induce ascites. Body weight and feed conversion ratio were measured weekly. The incidences of ascites and other disease were recorded to determine ascites morbidity and total mortality. Blood samples were taken on d 14, 21, 28, 35 and 42 to measure the plasma malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). On d 42, samples were taken to determine the right/total ventricular weight ratio (RV/TV), vessel wall area/vessel total area ratio (WA/TA) and mean media thickness in pulmonary arterioles (mMTPA). Low-temperature treatment increased plasma MDA concentration. When broilers were exposed to a cool environment for 3 weeks, plasma SOD and GSH-Px activity were decreased compared with normal-temperature chicks. RV/TV, WA/TA and mMTPA on d 42 were increased in birds exposed to cold, consistent with the increased pulmonary hypertension and ascites morbidity. Early feed restriction markedly decreased plasma MDA concentration. The plasma SOD and GSH-Px activity of feed-restricted birds were markedly higher than those fed ad libitum on d 35 and d 42. All early feed restriction treatments reduced ascites morbidity and total mortality. On d 42, the RV/TV, WA/TA and mMTPA of feed-restricted broilers were lower than that of the ad libitum-fed broilers. The results suggested that early feed restriction alleviated the lipid peroxidation, promoted the activity of enzymatic antioxidant and inhibited pulmonary vascular remodelling. These changes might be associated with reduced ascites incidence.     

Reduced erythrocyte deformability as a possible contributing factor to pulmonary hypertension and ascites in broiler chickens.

Deformability of erythrocytes and hematological parameters in white leghorn and broiler chickens were measured at age 7, 14, 21, 28, and 35 days. For deformability testing, a simple vertical apparatus containing a polycarbonate membrane with 5-microns pores was used. This technique assesses erythrocyte deformability by measuring the filtration time of an erythrocyte suspension through the pores. There was a significant difference in filtration time between the leghorns and broilers at all sampling times. These results indicate that reduced erythrocyte deformability in broilers may be one of the predisposing factors that increase resistance to blood flow and alter the rheology of blood in the microcirculation in the lung. Increased resistance to flow may result in pulmonary hypertension, heart failure, and ascites in broiler chickens.     

Blood volume increase in salt-induced pulmonary hypertension, heart failure and ascites in broiler and White Leghorn chickens.

In this study we tested the hypothesis that excess dietary salt produces an expansion of extracellular fluid volume which may be associated with pulmonary hypertension-induced right ventricular failure in chickens with rapid growth rates. One-week-old broiler and White Leghorn chickens were given 0.5% salt in their drinking water for three weeks. Saline water had a minimal effect on White Leghorns. The hypothesis appears to be correct since salt-treatment in broilers resulted in up to 30% expansion in blood volume and there was 50% mortality from pulmonary hypertension-induced right ventricular failure and ascites. There was marked (up to 88% in some broilers) right ventricular hypertrophy, an indicator of pulmonary hypertension. There was less left ventricular hypertrophy as shown by an increase in the ratio of the right to total ventricle weight. There was up to 32% decrease in growth rate. There was renal hypertrophy in the salt-treated birds as shown by a higher kidney to body weight ratio.     

Nitric oxide synthase expression in the endothelium of pulmonary arterioles in normal and pulmonary hypertensive chickens subjected to chronic hypobaric hypoxia

To determine whether or not exposure to chronic hypoxia and subsequent development of pulmonary hypertension syndrome (PHS) induce alterations in endothelial nitric oxide (NO) production in broiler's pulmonary vascular bed of broilers, we studied the expression of nitric oxide synthase enzyme in pulmonary endothelial cells by a nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemical staining reaction. For this purpose, 60 broilers of three different ages (17, 30, and 42 days) were used. The animals were distributed in two groups: a) 30 healthy (nonhypertensive) broilers and b) 30 chicks with PHS. All broilers in group b had fewer NADPH-diaphorase-positive endothelial cells in arterioles than did the nonhypertensive broilers. These differences were highly significant (P < 0.01). These results demonstrate for, the first time in broilers, that hypoxia-induced pulmonary hypertension is associated with a decrease of endothelial-derived NO expression in pulmonary vessels.     

Whole blood and plasma viscosity values in normal and ascitic broiler chickens.

1. Whole blood and plasma viscosity values in normal and ascitic broiler chickens were measured. 2. The mean blood viscosity value in ascitic broilers was greater than that of the controls. There was a small but significant difference in the opposite direction between plasma viscosity values of the respective groups of birds. 3. Although the haematocrit and arterial pressure index values in the ascitic birds were raised, there was a fall in the concentration of total plasma protein. 4. The data suggest that the raised viscosity in the ascitic birds was caused by a polycythemia and not by any influence of plasma protein. 5. The cumulative effect of these factors, such as raised blood viscosity values and larger deformed red cells flowing through constricted lung arterioles, may contribute to the pulmonary hypertension and ascites seen in some young commercial broilers.     

Effect of dietary flax oil and hypobaric hypoxia on right ventricular hypertrophy and ascites in broiler chickens

1. The effect of dietary flax oil on growth rate, blood haemoglobin content, mortality and incidence of pulmonary hypertension and ascites in broilers at ambient pressure and at reduced atmospheric pressure was examined.

2. Birds were housed either in hypobaric chambers simulating 1000, 1500 or 2200 m altitude or in pens at ambient atmospheric pressure and fed on diets containing 100 g/kg added fat as either an animal/vegetable (A/V) blend or flax oil.

3. Birds raised under hypobaric conditions had a decreased growth rate and increased mortality, blood haemoglobin content, and incidence of pulmonary hypertension and ascites compared to the groups at normal atmospheric pressure.

4. Broilers fed on the diet containing flax oil snowed no difference in growth rate or blood haemoglobin content compared to birds fed on the A/V fat diet raised at the same altitude.

5. Inclusion of flax oil in the diet decreased mortality and the incidence of ascites at 2200 m and pulmonary hypertension at 1500 m.

6. Flax oil may be an effective method of reducing ascites and pulmonary hypertension in broilers without affecting performance.     

Vascular remodeling and its role in the pathogenesis of ascites in fast growing commercial broilers

This study examined the putative role of blood vessel pathology in the development of ascites in broilers. Major blood vessels (aorta, brachiocephalic arteries, pulmonary arteries, and vena cava) from normal commercial male broiler chickens, and broilers that developed congestive heart failure (CHF) with or without ascites were subjected to gross and microscopic examination.On cross-section, grossly, the arteries from normal broilers and those showing dilated cardiomyopathy without ascites appeared circular, with firm wall tone characteristic of the normal artery. In contrast, the arteries from ascitic broilers appeared flaccid and lacked elasticity, which was evidenced by collapsing, ellipsoid cross-sectional arterial lumen owing to the structural weakness of the arterial walls. Microscopically, ascitic broilers showed thinning or occasionally total loss of elastic elements in the arterial wall, and reduced network density of the structural matrix of the vascular wall, as well as increased thickness of fibers in vena cava.The structural changes seen in the major arteries from ascitic broilers are maladaptive, and as such would definitively impose an increased hemodynamic burden on the already failing heart pump. The changes in veins are indicative of pathological remodeling conducive to increased permeability of the vascular wall, particularly in the situation when a poorly distensible structure is further subjected to wall stress associated with increased pressure and volume overload. Taken together, increased hemodynamic burden and reduced structural density of the venous wall constitute conditions conducive for seepage and accumulation of ascitic fluid.     

Sodium hydrosulfide prevents hypoxia-induced pulmonary arterial hypertension in broilers

1. The aim of the study was to determine if H₂S is involved in the development of hypoxia-induced pulmonary hypertension in broilers, a condition frequently observed in a variety of cardiac and pulmonary diseases.

2. Two-week-old broilers were reared under normoxic conditions or exposed to normobaric hypoxia (6?h/day) with tissue levels of H₂S adjusted by administering sodium hydrosulfide (NaHS, 10?µmol/kg body weight/day). Mean pulmonary arterial pressure, right ventricular mass, plasma and tissue H₂S levels, the expression of cystathionine-β-synthase (CSE) and vascular remodeling were determined at 35?d of age.

3. Exposure to hypoxia-induced pulmonary arterial hypertension was characterized by elevated pulmonary pressure, right ventricular hypertrophy and vascular remodeling. This was accompanied by decreased expression of CSE and decreased concentrations of plasma and tissue H₂S.

4. Hypoxia-induced pulmonary hypertension was significantly reduced by administration of NaHS but this protective effect was largely abolished by D, L-propargylglycerine, an inhibitor of CSE.

5. The results indicate that H₂S is involved in the development of hypoxia-induced pulmonary hypertension. Supplementing NaHS or H₂S could be a strategy for reducing hypoxia-induced hypertension in broilers.     

L-arginine prevents reduced expression of endothelial nitric oxide synthase (NOS) in pulmonary arterioles of broilers exposed to cool temperatures

This study investigated nitric oxide synthase (NOS) expression in the endothelium of pulmonary arterioles of broilers during the development of pulmonary hypertension syndrome (PHS). PHS was triggered by exposing broilers to sub-thermoneutral (cool) temperatures and an additional 1.0% L-arginine was added to the basal diet to evaluate the effects of supplemental L-arginine on nitric oxide (NO) production, endothelial NOS expression, and the incidence of PHS. Cumulative mortality from PHS, right/total ventricle weight ratios (RV/TV), and body weights were recorded. Plasma NO concentration and NOS expression in the endothelium of pulmonary arterioles with an outer diameter ranging from 100 to 200 microm were determined. Birds exposed to cool temperatures had increased pulmonary hypertension and PHS mortality and diminished endothelial NOS expression. Supplemental dietary L-arginine reduced PHS mortality and elicited higher NOS expression within the pulmonary endothelium coincident with elevated NO production. The results demonstrated that broilers developing PHS exhibited diminished NOS expression in the endothelium of their pulmonary arterioles. Supplemental L-arginine prevented the reduced expression of NOS in the pulmonary endothelium, which might contribute to the increased production of NO by the pulmonary vasculature.     

Dietary N,N‐dimethylglycine supplementation improves nutrient digestibility and attenuates pulmonary hypertension syndrome in broilers

N,N‐dimethylglycine (DMG) is an intermediary metabolite in cellular choline and betaine metabolism. The present trial aimed to evaluate the effect of dietary DMG on nutrient digestibility and development of pulmonary hypertension syndrome in broilers. A total of 64 14‐day‐old broiler hens (Ross‐308) were raised until age 40 days under cold environmental temperature conditions (15 °C) and were fed a high energy feed in order to incite pulmonary hypertension. Birds were randomly assigned to two groups of which each group had eight replicate pens of four birds each. Test diets contained 0 or 167 mg Na‐DMG (Taminizer^® D; Taminco N.V., Ghent, Belgium)/kg feed. N,N‐dimethylglycine supplementation resulted in a significant improvement in apparent faecal digestibility of crude protein and nitrogen‐free extract. Further, fulminant ascites was numerically lowered by DMG and incidence of pulmonary hypertension decreased significantly from 44.8% in the control group to 14.6% in the DMG group. Finally, fasted plasma level of non‐esterified fatty acids (NEFA) was twofold in the control group in relation to the DMG group. In conclusion, these data demonstrate beneficial effects of DMG on digestibility of non‐fat fractions, on fat metabolism and on progression towards broiler ascites syndrome.     

The relationship of right ventricular hypertrophy, right ventricular failure, and ascites to weight gain in broiler and roaster chickens

Nine hundred twenty-five male progeny from 50 sire families of a commercial sire line were weighed at 14, 28, and 47 days and scored for right ventricular hypertrophydilation at 48 days. Broilers with marked hypertrophy of the right ventricle at processing (298 of 925) were significantly heavier than their more normal contemporaries at 14 and 28 days of age. These results suggest that rapidly growing broilers are more susceptible to increased pulmonary arterial pressure resulting in right ventricular hypertrophy, right ventricular failure, and ascites than slower-growing broilers. Thirty-five (3.5% of 997) broilers died from right ventricular failure and ascites, and 14 (1.5% of 925) has ascites at processing. Two hundred fifty-nine sibs were kept on full feed to 16 weeks of age. Between 7 and 16 weeks, 68 (26.3%) of these cockerels died from right ventricular failure and ascites and a further 27 (10.4%) had marked right ventricular hypertrophy-dilation when processed at 16 weeks. Thus most of the 298 broilers classified as having marked right ventricular hypertrophy at 7 weeks would likely have died from right ventricular failure and ascites if they had been kept on full feed until 16 weeks.     

Effect of L-NAME on pulmonary arterial pressure,plasma nitric oxide and pulmonary hypertension syndrome morbidity in broilers

1. Experiments were conducted to evaluate the effect of a synthetic inhibitor of nitric oxide (NO) synthase (L-NAME) on pulmonary arterial pressure (PAP) and pulmonary hypertension syndrome (PHS) morbidity in broilers. 2. In Experiment 1, broilers were infused intravenously with L-NAME, and the mean pulmonary arterial pressure (mean PAP) and plasma NO were measured at 0, 1, 2 and 4 h after the start of infusion. The mean PAP increased and plasma NO was reduced at 1 to 2 h in broilers treated with L-NAME. 3. In Experiment 2, 180 Arbor Acres broilers were evenly divided into three groups: a control group (group C), and two groups exposed to low environmental temperatures and fed a 3, 3, 5-triiodothyronine (T3) supplemented diet alone (group A) or also including 100 ppm L-NAME (group B). 4. The PHS morbidity of group A was higher than for group C but lower than for group B. Plasma endothelin-1 was higher in broilers in groups A and B than in group C. Plasma NO was not significantly lower in broilers of group B when compared with those in group A. 5. The right/total ventricular weight ratio (RV/TV) and mean PAP were higher in groups A and B than in group C, and the RV/TV ratio increased one week earlier in group B than in group A. 6. These results suggest that L-NAME increases broiler PAP by inhibiting the endogenous synthesis of NO, leading to pulmonary hypertension, right ventricular hypertrophy and the increased morbidity of PHS in broilers.