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. 2020 Jul;99(7):3363-3373.
doi: 10.1016/j.psj.2020.03.015. Epub 2020 Apr 17.

Dietary supplementation of 25-hydroxycholecalciferol improves cardiac function and livability in broiler breeder hens-amelioration of blood pressure and vascular remodeling

Yo-Lin Yeh  1 , Pao-Chia Chou  2 , Yu-Hui Chen  1 , Lih-Shiuh Lai  2 , Thau Kiong Chung  3 , Rosemary L Walzem  4 , San-Yuan Huang  5 , Shuen-Ei Chen  6
Affiliations

Dietary supplementation of 25-hydroxycholecalciferol improves cardiac function and livability in broiler breeder hens-amelioration of blood pressure and vascular remodeling

Yo-Lin Yeh et al. Poult Sci. 2020 Jul.

Abstract

A supplement of 69 μg 25-hydroxycholecalciferol (25-OH-D3)/kg feed suppressed the mortality in feed-restricted broiler breeder hens and in hens allowed ad libitum feed intake (Ad-hens) in a feeding trial from age 26 to 60 wk. Outcomes for the mechanisms found that 25-OH-D3 relieved systemic hypoxia, pathological cardiac remodeling and arrhythmias, and hepatopathology to improve hens' livability. In the study, we further evaluated the effect of 25-OH-D3 on blood pressure and vascular remodeling relative to cardiac pathogenesis of sudden death (SD). Ad libitum feed intake increased mechanical loading and contributed to maladaptive cardiac hypertrophy as evidenced by consistently elevated peripheral arterial blood pressure in Ad-hens before SD (P < 0.05). In planned longitudinal measurements, Ad-hens also showed higher right ventricle systolic pressure and right ventricle diastolic pressure (RVDP) (P < 0.05). Supplemental 25-OH-D3 relieved peripheral hypertension and prevented time-dependent increases of RVDP in Ad-hens through the renin-angiotensin system and circulating nitric oxide availability and by regulating vascular remodeling including elastin/collagen ratio and smooth muscle cell proliferation in the pulmonary artery for improved elasticity/stiffness (P < 0.05). The antihypertensive effect via the renin-angiotensin system and nitric oxide regulation in respect to heart rate and arrhythmias by 25-OH-D3 were further confirmed in 51 week-old feed-restricted broiler breeder hens challenged with salt loading for 5 wk. Despite feed restriction, the most feed-efficient hens of feed-restricted groups also exhibited cardiac pathological hypertrophy, in conjunction with higher right ventricle systolic pressure, RVDP, plasma nitric oxide levels, and more dramatic arterial remodeling (P < 0.05). These results suggest that peripheral and pulmonary hypertension are the key drivers of SD and that 25-OH-D3 is an effective antihypertensive supplement to alleviate cardiac pathogenesis and improve livability in broiler breeder hens.

Keywords: 25-hydroxycholecalciferol; broiler breeder hen; cardiac hypertrophy; hypertension; vascular remodeling.

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Figures

Figure 1
Figure 1
Longitudinal effect of dietary 25-OH-D3 supplementation on peripheral blood pressure of broiler breeder hens provided with restricted or ad libitum feed intake. At age of 29 wk, 10 hens from each group were selected for peripheral blood pressure monitoring. The measurements were continued with the selected hens surviving to 35, 47, or 60 wk of age. Results were separated to provide outcomes for hens surviving to 60 wk of age (survivors for R, R + 25-OH-D3, Ad, and Ad+25-OH-D3, n = 8, 8, 3, and 5, respectively) and those of hens experiencing sudden death (n = 2, 2, 7, and 5 at 29 wk, n = 2, 2, 5, and 4 at 35 wk, and n = 1, 1, 2, and 2 at 47 wk, respectively). ∗Significant difference owing to feeding level (vs. corresponding R-hens, P＜0.05). Abbreviations: +, significant difference by 25-OH-D3 inclusion (vs. corresponding R- or Ad-hens, P＜0.05); ˆ, significant difference vs. hens survived at the same age with the same treatment (P＜0.05); R, restriction; Ad, ad libitum; 25-OH-D3, 25-hydroxycholecalciferol.
Figure 2
Figure 2
Effect of dietary 25-OH-D3 supplementation on RAAS and plasma nitric oxide level of broiler breeder hens provided with restricted or ad libitum feed intake. When hens were 29, 35, and 47 wk of age, 4, 7, and 7 hens from each group, respectively, were sampled for tissue collection. Angiotensin II and nitric oxide concentrations were measured in in plasma, whereas ACE and renin mRNA expression were measured in lungs and kidney, respectively, through qRT-PCR method. Results of qRT-PCR were normalized to β-actin and expressed as ratios relative to R-hens at 29 wk ∗Significant difference by feeding level (vs corresponding R-hens, P ＜ 0.05). a–cMeans with different letter differ significantly among ages within the same treatment (P < 0.05). Abbreviations: +, significant difference by 25-OH-D3 inclusion (vs. corresponding R- or Ad-hens, P ＜ 0.05); R, restriction; Ad, ad libitum; 25-OH-D3, 25-hydroxycholecalciferol; ACE, angiotensin-converting enzyme; qRT-PCR, quantitative real time polymerase chain reaction; RAAS, renin–angiotensin–aldosterone system.
Figure 3
Figure 3
Effect of dietary 25-OH-D3 supplementation on right atrial pressure of broiler breeder hens provided with restricted or ad libitum feed intake. When hens were 29, 35, and 47 wk of age, 4, 7, and 7 hens from each group, respectively, were sampled for tissue collection. Immediately before necropsy, selected hens were used for right ventricle pressure measurement. ∗Significant difference by feeding level (vs. corresponding R-hens, P＜0.05). Means with different letters differ significantly among ages within the same treatment (P＜0.05). Abbreviations: R, restriction; Ad, ad libitum; 25-OH-D3, 25-hydroxycholecalciferol.
Figure 5
Figure 5
Effect of dietary 25-OH-D3 supplementation on pulmonary artery dimension and thickness of broiler breeder hens provided with restricted or ad libitum feed intake. When hens were 29, 35, and 47 wk of age, 4, 7, and 7 hens from each group, respectively, were sampled for tissue collection. Pulmonary artery histology was determined at 35 and 47 wk. The midsection of the pulmonary artery (1/2 of the whole length), 3/4 length above (distal) or below (proximal) the middle line were used for lumen diameter and wall thickness measurements. Results represent an average of 8 measurements at every 45∘angle around the circumference of the artery (8 points). ∗Significant difference by feeding level (vs. corresponding R-hens, P＜0.05). Abbreviations: +, significant difference by 25-OH-D3 inclusion (vs. corresponding R- or Ad-hens, P＜0.05); R, restriction; 25-OH-D3, 25-hydroxycholecalciferol.
Figure 4
Figure 4
Effect of dietary 25-OH-D3 supplementation on arterial remodeling of broiler breeder hens provided with restricted or ad libitum feed intake. When hens were 29, 35, and 47 wk of age, 4, 7, and 7 hens from each group, respectively, were sampled for tissue collection. Pulmonary artery histopathology was determined at 35 and 47 wk. The midsection of the pulmonary artery (1/2 of the whole length) was used for Trichrome Masson and Verhoeff's staining. Connective tissue (collagens) stains blue with fibrosis (panel A), smooth muscle cells stain purple staining (panel A), and elastin stains brown (panel B). In the histology, a well-arranged structure with neatly stacked layers by 25-OH-D3 was noted in both R- and Ad-hens (panel A, left). Quantification of the intensity was made using ImageJ (panel C) and results were expressed as a ratio relative to R-group at 35 wk. Four images per section were used for quantification. ∗Significant difference by feeding level (vs. corresponding R-hens, P＜0.05). +Significant difference by 25-OH-D3 inclusion (vs. corresponding R- or Ad-hens, P＜0.05). #Significant difference vs. corresponding counterparts at 35 wks (P＜0.05). Abbreviations: R, restriction; 25-OH-D3, 25-hydroxycholecalciferol.
Figure 6
Figure 6
Right ventricle pressure, plasma nitric oxide level, and arterial remodeling of feed-restricted broiler breeder hens with normal or pathological cardiac hypertrophy at necropsy. At age of 29, 35, and 47 wk, 4, 7, and 7 hens from each group, respectively, were sampled for tissue collection. Immediately before necropsy, selected hens were used for right ventricle pressure measurement. None of the birds in R-groups at age of 29 wk, but 2 hens from each group exhibited pathological cardiac hypertrophy (concentric and eccentric) at 35 and 47 wk. Results thus were regrouped and presented according to normal (n = 10) or pathologic cardiac hypertrophy (n = 4). ∗Significant difference vs. normal hens (P＜0.05). Abbreviations: NO, nitric oxide; SMC, smooth muscle cells; 25-OH-D3, 25-hydroxycholecalciferol.
Figure 7
Figure 7
Dietary 25-OH-D3 supplementation ameliorates blood pressure, plasma angiotensin II and nitric oxide (NO) levels, and cardiac functional compromise induced by salt loading in broiler breeder hens with high salt loading. At age of 51 wk, additional 4 hens from the R and R + 25-OH-D3 group were challenged with salt loading in drinking water (0.2% NaCl in distilled water) and another 4 R-hens provided with distilled water as a comparative control. Peripheral blood pressure, heart rate, ECG, plasma angiotensin II, and (NO) concentration measurements were made 1, 3, and 5 wks after treatment. ∗Significant difference by NaCl loading (vs. control, P＜0.05). Abbreviations: +, significant difference by 25-OH-D3 inclusion (vs. NaCl group, P＜0.05); R, restriction; 25-OH-D3, 25-hydroxycholecalciferol; ECG, electrocardiography; QTc, interval corrected QT interval in ECG profile.
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