Sleep hormone melatonin protects heart, lungs in PAH rat study
Daily treatment prevents narrowing of lung blood vessels
Written by |
Daily treatment with the sleep hormone melatonin prevented the narrowing of the lung’s blood vessels, the underlying cause of pulmonary arterial hypertension (PAH), in a rat study.
Melatonin also prevented signs of heart injury and neutralized reactive oxygen species (ROS), chemically reactive molecules that can damage cells.
“These data reinforce the therapeutic potential of melatonin for the heart,” the researchers wrote.
The study,”Cardioprotective effects of melatonin in vitro and in two in vivo models of heart disease: Isoproterenol-induced cardiac injury and pulmonary hypertension,” was published in Toxicology and Applied Pharmacology.
In PAH, small lung arteries narrow and thicken, raising blood pressure and forcing the right side of the heart to work harder. Without treatment, PAH can lead to heart failure.
Melatonin and PAH
Melatonin is known for its role in sleep and the body’s circadian rhythm. Earlier studies have described it as a promising therapeutic agent for cardiac diseases. Melatonin can neutralize ROS, and it has anti-inflammatory properties.
However, no studies have compared melatonin’s effects in animal models of PAH and heart injury.
To create a PAH animal model, researchers injected male rats with monocrotaline, a chemical that triggers inflammation and arterial wall thickening. In this model, high pulmonary blood pressure severely impairs the right ventricle, one of the heart’s lower chambers.
The team administered daily melatonin (10 mg/kg/day) via a tube into the stomach, then assessed the heart and pulmonary artery using echocardiography 21 days later.
Without treatment, pulmonary artery diameter and the area inside the blood vessel decreased in PAH rats, indicating thickened, narrowed blood vessels. This group also had a higher myocardial performance index, a sign of poorer overall heart function. Daily melatonin treatment prevented these changes.
Despite benefits to the pulmonary arteries, the researchers saw no melatonin-related changes in the width of the right ventricle during a heartbeat (at its widest point) or between heartbeats, when the heart muscle relaxes.
Tests found higher levels of xanthine oxidase, an enzyme that produces ROS in the heart, in the right ventricles of the PAH rats than in healthy controls. In the PAH plus melatonin group, its production was lower than in the PAH group and comparable to that of healthy controls.
The researchers created a heart-injury model by giving rats isoproterenol, a drug that decreases left ventricular output, the total volume of blood pumped by the heart’s lower left chamber per minute. It also triggers inflammation and scarring. Rats received the same melatonin regimen as in the PAH model.
In heart-injured rats treated with melatonin, left ventricular output was comparable to that in healthy rats. Melatonin also prevented a decrease in left ventricular width during and between heartbeats. However, tissue examination found no difference in inflammation or scar formation.
“Melatonin administration failed to reverse [tissue] inflammatory infiltration and fibrosis [scarring] despite improving echocardiographic [left ventricular] functional parameters,” which may reflect “the limited sensitivity of [tissue] analysis,” the researchers wrote.
Even so, the production of NLRP3, a protein complex involved in inflammation and cell death, was lower in the isoproterenol plus melatonin group than in both the isoproterenol and healthy control groups.
The researchers then exposed immature heart muscle cells to hydrogen peroxide, a type of ROS, which reduced cell viability (the proportion of live, healthy cells). In cells pre-treated with melatonin, viability remained lower than in the control group but higher than in the hydrogen peroxide-only group.
Hydrogen peroxide exposure also decreased the levels of antioxidant sulphydryl groups. As with viability, cells pre-treated with melatonin had higher levels of these antioxidants than the hydrogen peroxide-only group, but lower than the control group.
Staining to separate living cells from dead or dying cells yielded consistent findings. The melatonin plus hydrogen peroxide group had a higher percentage of living cells and a lower percentage of dead cells than the hydrogen peroxide group. However, it still differed from the control group.
“Although further studies are needed to translate these findings to patients with cardiac disease, the present study reinforces the therapeutic potential of melatonin for the heart under different pathological [disease-related] conditions,” the team concluded.
Leave a comment
Fill in the required fields to post. Your email address will not be published.