Circulating Concentrations of Key Regulators of Nitric Oxide Production in Undernourished Sheep Carrying Single and Multiple Fetuses

Abstract

The aim of this study was to investigate the blood concentrations of L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine, which are regulators of nitric oxide (NO) synthesis, in single, twin, and triplet pregnancies in ewes undergoing either a dietary energy restriction or receiving 100% of their energy requirements. From day 24 to 100 of pregnancy, the ewes were fed ryegrass hay and two different iso-proteic concentrates fulfilling either 100% of ewes’ energy requirements (control group; n = 30, 14 singleton pregnancies, 12 twin pregnancies, and 4 triplet pregnancies) or only 45% (feed-restricted group; n = 29; 11 singleton pregnancies, 15 twin pregnancies, and 3 triplet pregnancies). Blood samples were collected monthly to measure, by capillary electrophoresis, the circulating concentrations of arginine, ADMA, homoarginine, SDMA, and of other amino acids not involved in NO synthesis to rule out possible direct effects of diet restriction on their concentrations. No differences between groups were observed in the circulating concentrations of most of the amino acids investigated. L-homoarginine increased markedly in both groups during pregnancy (p < 0.001). SDMA (p < 0.01), L-arginine, and ADMA concentrations were higher in feed-restricted ewes than in controls. The L-arginine/ADMA ratio, an indicator of NO production by NOS, decreased towards term without differences between groups. The ADMA/SDMA ratio, an index of the ADMA degrading enzyme activity, was higher in controls than in feed-restricted ewes (p < 0.001). Obtained results show that circulating concentrations of L-arginine, of its metabolites, and the ratio between NO synthesis boosters and inhibitors are altered in energy-restricted ewes, and that these alterations are more marked in ewes carrying multiple fetuses.

Nitric Oxide Synthase Is Involved in Follicular Development via the PI3K/AKT/FoxO3a Pathway in Neonatal and Immature Rats

“…Furthermore, L-Arg promoted NO generation and induced advanced follicular development. This is consistent with the finding that the ratio between NO synthesis boosters and inhibitors is higher in ewes carrying multiple fetuses [49].…”

Effects of Zinc Oxide and Arginine on the Intestinal Microbiota and Immune Status of Weaned Pigs Subjected to High Ambient Temperature

“…The mRNA expression levels of HSP27 in the livers were remarkably decreased in pigs fed P-Zn, ZnArg1, ZnArg2, and ZnArg3 diets compared with the Con treatment. The positive correlation between HSP expression and stress was previously reported in other studies [2,4,13]. The low gene expression of HSP27 in the liver and a tendency for lower blood cortisol in the ZnArg2 and ZnArg3 treatments may indicate a lower stress level compared with the Con treatment.…”

“…The health condition of piglets is highly unstable at weaning because of the stress of changing feed form, separation from the mother sow, and changes in the physical environment [1][2][3]. These stressors may cause dysbiosis due to sudden microbial changes in the intestine [1,4].…”

“…Therefore, stressors such as microbial change, heat stress, and sepsis dramatically increase the Arg requirements [10,12,13]. Arginine plays a crucial role in the production of polyamine and NO, which are strong anti-stress and vasodilator factors in mammals [2]. In addition, Arg facilitates the provision of cellular signaling, intestinal recovery, and immunity factors [10,14].…”

N-carbamylglutamate and L-arginine Supplementation Improve the Intestinal Oxidative Resistance of the Intrauterine Growth-retarded Ovine Fetuses 

“…Particularly, Arg enhances the synthesis of NO in normal conditions within the small intestine (Weckman et al, 2019), thus, it exerts a vital part in regulating the antioxidant defense (Liang et al, 2018). Recent evidence emphasized the importance of arginine/NO pathway during pregnancy as indicated by the increase in the circulating levels of arginine and its metabolites in feed-restricted ewes bearing multiple-fetuses (Berlinguer et al, 2020). However, whether maternal dietary Arg or NCG supplementation during IUGR alters fetal small intestine redox status is unclear.…”