Hypotensive effects of melatonin in rats: Focus on the model, measurement, application, and main mechanisms

The hypotensive effects of melatonin are based on a negative correlation between melatonin levels and blood pressure in humans. However, there is a positive correlation in nocturnal animals that are often used as experimental models in cardiovascular research, and the hypotensive effects and mechanism of melatonin action are often investigated in rats and mice. In rats, the hypotensive effects of melatonin have been studied in normotensive and spontaneously or experimentally induced hypertensive strains. In experimental animals, blood pressure is often measured indirectly during the light (passive) phase of the day by tail-cuff plethysmography, which has limitations regarding data quality and animal well-being compared to telemetry. Melatonin is administered to rats in drinking water, subcutaneously, intraperitoneally, or microinjected into specific brain areas at different times. Experimental data show that the hypotensive effects of melatonin depend on the experimental animal model, blood pressure measurement technique, and the route, time and duration of melatonin administration. The hypotensive effects of melatonin may be mediated through specific membrane G-coupled receptors located in the heart and arteries. Due to melatonin's lipophilic nature, its potential hypotensive effects can interfere with various regulatory mechanisms, such as nitric oxide and reactive oxygen species production and activation of the autonomic nervous and circadian systems. Based on the research conducted on rats, the cardiovascular effects of melatonin are modulatory, delayed, and indirect.