Abstract
The pineal hormone, melatonin (N-acetyl-5-methoxytryptamine), shows potent receptor-dependent and -independent actions, which participate in blood pressure regulation. The antihypertensive effect of melatonin was demonstrated in experimental and clinical hypertension. Receptor-dependent effects are mediated predominantly through MT1 and MT2 G-protein coupled receptors. The pleiotropic receptor-independent effects of melatonin with a possible impact on blood pressure involve the reactive oxygen species (ROS) scavenging nature, activation and over-expression of several antioxidant enzymes or their protection from oxidative damage and the ability to increase the efficiency of the mitochondrial electron transport chain. Besides the interaction with the vascular system, this indolamine may exert part of its antihypertensive action through its interaction with the central nervous system (CNS). The imbalance between the sympathetic and parasympathetic vegetative system is an important pathophysiological disorder and therapeutic target in hypertension. Melatonin is protective in CNS on several different levels: It reduces free radical burden, improves endothelial dysfunction, reduces inflammation and shifts the balance between the sympathetic and parasympathetic system in favor of the parasympathetic system. The increased level of serum melatonin observed in some types of hypertension may be a counter-regulatory adaptive mechanism against the sympathetic overstimulation. Since melatonin acts favorably on different levels of hypertension, including organ protection and with minimal side effects, it could become regularly involved in the struggle against this widespread cardiovascular pathology.
Highlights
Essential hypertension is a complex hemodynamic and structural disorder, whose underlying mechanisms involve several familiar pathogenic factors
Subjects with attenuated BP decline, non-dippers or those with nocturnal hypertension have increased risk of cardiovascular events compared to the common population [110], and nocturnal blood pressure has even been identified as a better predictor of cardiovascular outcome than daily BP values [111]
It has been shown in our laboratory that melatonin level in the pineal gland was increased in L-NAME–induced hypertension compared to controls
Summary
Essential hypertension is a complex hemodynamic and structural disorder, whose underlying mechanisms involve several familiar pathogenic factors. If the endothelium inflammation in the variable parts of the central nervous system is involved in the pathogenesis of hypertension in a more general way, substances with a potential anti-inflammatory, antioxidant and endothelium-protecting action in the central nervous system (CNS), such as melatonin, might become important players in the therapeutic targeting. The mechanisms and pathways involved in its BP lowering action are complex and not entirely clear. Both effects, mediated by specific melatonin receptors and direct unspecific actions, those involving the antioxidant nature of melatonin, are of significant biological value. The ability of melatonin to potentiate the antioxidant action of substances with an antioxidant potential, like glutathione, vitamin E and vitamin C, may contribute to better vascular functions and blood pressure regulation [26,27,28]
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