Liraglutide Enhances the Activity of the ACE-2/Ang(1–7)/Mas Receptor Pathway in Lungs of Male Pups from Food-Restricted Mothers and Prevents the Reduction of SP-A

Abstract

In utero growth restriction and being born small for gestational age are risk factors for respiratory morbidity. IUGR (in utero growth retardation) is associated to overall reduction in lung weight, surfactant content and activity, impaired maturation of the alveolar type II cells, and decreased alveolar formation. The renin-angiotensin system (RAS) may be a key target underlying pathophysiological lung alterations. GLP-1 and agonists of its receptor modulate the expression levels of different components of RAS and also are very important for lung maturation and the production of surfactant proteins. The aim of this study was to elucidate the effects of IUGR induced by perinatal food restriction of the mother in the lung function of pups at early stages of life (PD21) and to determine if liraglutide had any effect during gestational period. Sprague-Dawley pregnant rats were randomly assigned to 50% food restriction (MPFR) or ad libitum control (CT) groups at day of pregnancy 12 (GD12). From GD14 to parturition, pregnant MPFR and CT rats were treated with liraglutide or vehicle. At postnatal day 21 and before weaning, 20 CT and 20 FR male pups were sacrificed and lungs were analyzed by RT-PCR. Liraglutide restored surfactant protein A (SP-A) mRNA expression in pup lungs from food-restricted mothers. Surfactant protein B (SP-B) mRNA expression is not affected by neither IUGR nor liraglutide treatment. Moreover, liraglutide modulated different elements of RAS, increasing angiotensin-converting enzyme 2 (ACE2) and MasR mRNA expression only in pups from food-restricted mothers (MPFR), despite food restriction had not any direct effect at this early stage. Liraglutide also increased endothelial nitric oxide synthase (eNOS) expression in MPFR lungs, reflecting the activation of MasR by angiotensin 1–7. In conclusion, liraglutide prevented the alteration in lung function induced by IUGR and promoted the positive effects of ACE2-Ang(1–7)-MasR in restoring lung function.

Liraglutide Attenuates Non-Alcoholic Fatty Liver Disease in Mice by Regulating the Local Renin-Angiotensin System

“…It has been reported that GLP-1 is closely linked to RAS in multiple organs (Zhang et al, 2015;Fandiño et al, 2018). Therefore, we investigated the liraglutide-mediated regulation of RAS system to identify the role of the RAS in NAFLD progression and improvement.…”

“…There is emerging evidence supporting an association between glucagon-like peptide-1/glucagon-like peptide-1 receptor (GLP-1/ GLP-1R) signaling and the RAS both in circulation and multiple local tissues (e.g., cardiovascular, lung, and kidney) (Zhang et al, 2015;Fandiño et al, 2018). As one of the most important incretins in the body, GLP-1 can exert hypoglycemic effects through various mechanisms, including promoting insulin secretion and islet beta cell proliferation, inhibiting apoptosis and glucagon secretion, suppressing appetite, and promoting satiety (Bifari et al, 2018).…”

Perinatal Undernutrition, Metabolic Hormones, and Lung Development

“…In addition, transplacental administration of the GLP-1R agonist liraglutide improved the morphology of the pulmonary vascular vessel in an animal model of congenital diaphragmatic hernia in rabbits [45]. Moreover, GLP-1R activation promoted a marked induction of the ACE2 expression, which enhanced the activity of the ACE2/Ang(1-7)/MasR branch of the renin-angiotensin system, with vasodilatory instead of vasoconstrictor properties, in an animal model of FGR by perinatal food restriction of the mothers [46]. This was also observed in diabetic rats, showing right ventricle hypertrophy, which is prevented by just one-week administration of liraglutide [47].…”

“…In vitro phosphatidylcholine secretion [43,44] In vivo SFTPs expression [42,46,47] Increase ACE2/Ang (1-7)/MasR branch of the renin-angiotensin system [46,47] Retinoic acid…”

Emerging Molecular Prospective of SARS-CoV-2: Feasible Nanotechnology Based Detection and Inhibition

“…et al, 2020). The integral membrane protein ACE2, which accommodates metallopeptidase domain (PD) and collectrin-like domain (CLD), controls vasoconstriction and blood pressure, and plays a vital role in antiproliferation through the maturation of angiotensinII (Ang II) to angiotensin 1-7 [Ang(1-7)], serves as an antagonist of type 1 angiotensin receptor (AT2-R) (Tikellis and Thomas, 2012;Fandiño et al, 2018). Researchers have provided dismaying evidence of T-cell infection by SARS-CoV-2.…”