Co-administration of Apelin and T4 Protects Inotropic and Chronotropic Changes Occurring in Hypothyroid Rats

Abstract

BackgroundOne of the most important thyroid hormone targets is the cardiovascular system. Hemodynamic changes, such as decreased resting heart rate (HR), myocardial contractility, and cardiac output, and increased diastolic pressure and systemic vascular resistance, have been observed in hypothyroid patients. Moreover, in these patients, ECG changes include sinus bradycardia and low voltage complexes (P waves or QRS complexes).ObjectiveThis study aimed at evaluating the prophylactic effect of apelin on HR changes and QRS voltage that occur in propylthiouracil (PTU)-induced hypothyroid rats.MethodIn this study, 48 adult male Wistar rats weighing 170-235g were randomly divided into 6 groups: Control group (normal saline ip injection + tap water gavage); P group (PTU 0.05%, in drinking water); A group (apelin 200 µg.kg-1.day-1, ip); PA group [co-administration of PTU and apelin]; PT group [co-administration of PTU + T4 (0.2 mg/g per day, gavage)]; and PAT group (co-administration of PTU, apelin and T4). All experiments were performed for 28 consecutive days, and then the animals were anesthetized with an ip injection of ketamine (80 mg/kg) and xylazine (12 mg/kg). Lead II electrocardiogram was recorded to calculate HR and QRS voltage.ResultsHeart rate and QRS voltage increased more significantly in the hypothyroid group that consumed both apelin and T4 (201 ± 4 beat/min, 0.71 ± 0.02 mv vs. hypothyroid 145 ± 9 beat/min, 0.563 ± 0.015 mv; respectively).ConclusionThe co-administration of apelin and T4 showed a protective effect on QRS voltage and HR in PTU‑induced hypothyroid rats.

Serum irisin and apelin levels and markers of atherosclerosis in patients with subclinical hypothyroidism

“…Two studies have evaluated apelin levels in patients with SCH. In both studies no significant difference was observed in serum apelin levels between patients with SCH and healthy control subjects (10,13). The authors explained that these results were because, BMI was similar in both groups.…”

“…Arch Endocrinol Metab. 2019;63/1 and it was reported to be negatively associated with hypertensive heart disease (12,13). It was also shown to protect against ischaemia-reperfusion injury.…”

“…evaluated serum irisin levels after being euthyroid with levothyroxine treatment (15). Apelin was studied in patients with SCH (10,13), however it was also not evaluated after becoming euthyroid. Therefore in this study, we aimed to investigate serum irisin and apelin levelswhich were reported to be associated with increased cardiometabolic risk -in patients with SCH and the effect of levothyroxine therapy on these adipokines.…”

“…Apelin, an adipocytokine is a constituent of adipose tissue and is secreted by adipocytes that are stimulated by insulin. It is also an endogenous peptide that is a ligand for the APJ receptor and produced by endothelial cells in many parts of the body and the sites of receptor expression are linked to the different functions of apelin (13). It is a powerful inotrope and peripheral vasodilator and may be involved in fluid homeostasis, by its antidiuretic effect (27).…”

“…In addition a more recent study suggested that the apelin-APJ system might protect the myocardium from ischemia reperfusion injury by its actions on the reperfusion injury salvage kinase pathway (13). A small amount of evidence shows that the apelin-APJ system may be involved in modulating endothelial oxidative stress and the formation of coronary atherosclerotic plaques (27,28).…”