Deletion of the EGF receptor in vascular smooth muscle cells prevents chronic angiotensin II-induced arterial wall stiffening and media thickening.

AIM: In vivo vascular smooth muscle cell (VSMC) EGF receptor (EGFR) contributes to acute angiotensin II (AII) effects on vascular tone and blood pressure. The ubiquitously expressed EGFR has been implicated in vascular remodelling preceding end-organ damage by pharmacological inhibition, and AII signalling in cultured vascular cells is partly EGFR-dependent. However, the role of VSMC-EGFR in vivo during AII-induced pathophysiological processes is not known. METHODS: This study assesses the in vivo relevance of VSMC-EGFR during chronic AII challenge without further stressors, using a mouse model with inducible, VSMC-specific EGFR knock out (VSMC-EGFR-KO). In these mice functional and structural vascular, renal and cardiac effects or biomarkers were investigated in vivo and ex vivo. RESULTS: Vascular smooth muscle cell-EGFR-KO prevented AII-induced media hypertrophy of mesenteric arteries, renal arterioles and the aorta, VSMC ERK1/2-phosphorylation as well as the impairment of vascular compliance. Furthermore, induction of vascular fibrosis, creatinineamia, renal interstitial fibrosis as well as the increase in fractional water excretion was prevented. AII-induced increase in systolic blood pressure was mitigated. By contrast, endothelial dysfunction, induction of vascular inflammatory marker mRNA and albuminuria were not inhibited. Cardiac and cardiomyocyte hypertrophy were also not prevented by VSMC-EGFR-KO. CONCLUSION: Vascular smooth muscle cell-EGFRs are relevant for pathological AII action in vivo. Our data show in vivo and ex vivo the necessity of VSMC-EGFR for AII-induced structural and functional vascular remodelling, not including endothelial dysfunction. Hereby, VSMC-EGFR gains importance for complete AII-induced renal end-organ damage succeeding vascular remodelling.

Impact of ruminal pH on enteric methane emissions.

The objective of this study was to determine the impact of ruminal pH on methane (CH4) emission from beef cattle. Ruminal pH and CH4 data were generated in 2 experiments using 16 beef heifers offered high-forage (55% barley silage) or high-grain (92% concentrate; DM basis) diets. Both experiments were designed as a replicated 4 × 4 Latin square with 4 periods and 4 dietary treatments. Methane was measured over 4 consecutive days using open-circuit respiratory chambers with each chamber housing 2 heifers. The ruminal pH of individual heifers was measured using indwelling pH loggers. The mean ruminal pH and CH4 emission (g/h) of 2 heifers in every chamber were summarized in 30-min blocks. Even though rumen methanogens have been described to be inhibited by a pH < 6.0 in vitro, in vivo CH4-production rates (g/h) did not decrease when ruminal pH declined to threshold levels for subacute (5.2 ≤ pH < 5.5) or acute ruminal acidosis (pH < 5.2; P > 0.05). Daily mean CH4 emission (g/d) and ruminal pH were only mildly correlated (r2 = 0.27; P < 0.05), suggesting that additional factors, such as increased propionate formation or passage rate, account for the lower CH4 emissions from cattle fed high-grain as compared to high-forage diets. Lowering ruminal pH alone is, therefore, not an effective CH4-mitigation strategy. Mechanisms permitting methanogens to survive episodes of low-ruminal pH might include changes in community structure toward more pH-tolerant strains or sequestration into microenvironments within biofilms or protozoa where methanogens are protected from low pH.

Characterization of ruminal temperature and its relationship with ruminal pH in beef heifers fed growing and finishing diets.

This study characterized the relationship between ruminal temperature (T rum) and pH in beef cattle fed growing and finishing diets. In Exp. 1, 16 ruminally cannulated beef heifers (388.5 ± 34.9 kg BW) were fed 4 growing diets in a replicated 4 × 4 Latin square with four 21-d periods. Diets were (DM basis) grower control (CTLg; 35% barley grain plus 5% canola meal), 40% corn dried distillers grains plus solubles (CDDGSg), 40% wheat dried distillers grains plus solubles (WDDGSg), and 37.6% WDDGSg plus 2.4% corn oil (WDDGSg+O). All diets contained 55% barley silage (DM basis). Ruminal pH and T rum were continuously monitored for 4 d each period starting on d 18. In Exp. 2, the 16 heifers were gradually transitioned (529.1 ± 41.1 kg BW) from the growing diets to 1 of 4 finishing diets in a replicated 4 × 4 Latin square with four 28-d periods. Diets were (DM basis) finisher control (CTL f), 40% corn-based distillers grains plus solubles (CDDGS f), 40% wheat-based distillers grains plus solubles (WDDGS f), and 37.4% WDDGSf + 2.6% corn oil (WDDGS f+O). All finishing diets contained 8% barley silage (DM basis). Ruminal pH and T rum were measured from d 25 to 28. With growing diets (n = 64), maximum T rum was negatively related to minimum pH (P < 0.001, r = -0.53) and positively related to starch intake (P < 0.001, r = 0.55). Maximum T rum, T rum > 40°C (h/d), and area under the curve (AUC) T rum > 38°C (area × h/d) accounted for 28.3, 9.5, and 4.7%, respectively, of the variability in minimum pH (R(2) = 0.43, P < 0.001, n = 64). Mean T rum and maximum T rum were greater for CTL g than CDDGS g, WDDGS g, and WDDGS g+O. With finishing diets (n = 63), maximum T rum was negatively related to minimum ruminal pH (P < 0.001, r = -0.63) and positively related to DMI (P < 0.001, r = 0.62) and to starch intake (P < 0.001, r = 0.58). Maximum T rum, AUC T rum > 39°C, and duration T rum > 38°C accounted for 40, 17, and 3.6%, respectively, of the variability in minimum pH (R(2) = 0.60, P < 0.001, n = 63). Mean T rum and maximum T rum were greater for CTL f than CDDGS f, WDDGS f, and WDDGS f+O. When individual animal data were examined, heifers with duration T rum > 40°C did not necessarily have greater duration pH < 5.2 or pH < 5.5. Ruminal temperature has the potential to predict ruminal pH, likely owing to the biological relationship between acid production and the heat of fermentation. Exploitation of this relationship to predict pH could provide a means of overcoming the problems associated with long-term monitoring of ruminal pH using electrode-based approaches.

Effect of dried distillers grains plus solubles on enteric methane emissions and nitrogen excretion from growing beef cattle.

The objectives of this study were to examine the impact of corn- or wheat-based dried distillers grains with solubles (CDDGS or WDDGS) on enteric methane (CH4) emissions from growing beef cattle and determine if the oil in CDDGS was responsible for any response observed. Effects of CDDGS or WDDGS on total N excretion and partitioning between urine and fecal N were also examined in this replicated 4 × 4 Latin square using 16 ruminally cannulated crossbreed heifers (388.5 ± 34.9 kg of initial BW). The control diet contained (DM basis) 55% whole crop barley silage, 35% barley grain, 5% canola meal, and 5% vitamin and mineral supplement. Three dried distillers grains with solubles (DDGS) diets were formulated by replacing barley grain and canola meal (40% of dietary DM) with CDDGS, WDDGS, or WDDGS plus corn oil (WDDGS+oil). For WDDGS+oil, corn oil was added to WDDGS (4.11% fat DM basis) to achieve the same fat level as in CDDGS (9.95% fat DM basis). All total mixed diets were fed once daily ad libitum. Total collection of urine and feces was conducted between d 11 and 14. Enteric CH4 was measured between d 18 and 21 using 4 environmental chambers (2 animals fed the same diet per chamber). Methane emissions per kilogram of DM intake (DMI) and as percent of GE intake (GEI) among heifers fed WDDGS (23.9 g/kg DMI and 7.3% of GEI) and the control (25.3 g/kg DMI and 7.8% of GEI) were similar (P = 0.21 and P = 0.19) whereas heifers fed CDDGS (21.5 g/kg DMI and 6.6% of GEI) and WDDGS+oil (21.1 g/kg DMI and 6.3% of GEI) produced less (P < 0.05) CH4. Total N excretion (g/d) differed (P < 0.001) among treatments with WDDGS resulting in the greatest total N excretion (303 g/d) followed by WDDGS+oil (259 g/d), CDDGS (206 g/d), and the control diet (170 g/d), respectively. Compared with the control diet, heifers offered WDDGS, CDDGS, and WDDGS+oil excreted less fecal N (P < 0.001) but more (P < 0.001) urinary N. Results suggest that high-fat CDDGS or WDDGS+oil can mitigate enteric CH4 emissions in growing beef cattle. However, to completely assess the impact of DDGS on greenhouse gas emissions of growing feedlot cattle, the potential contribution of increased N excretion to heightened NH3 and nitrous oxide emissions requires consideration.