Melatonin, a Potential Therapeutic Agent for Smooth Muscle-Related Pathological Conditions and Aging

M.      J. Pozo; P.      J. Gomez-Pinilla; C.      Camello-Almaraz; F.      E. Martin-Cano; P.      Pascua; M.      A. Rol; D.      Acuna-Castroviejo; P.      J. Camello

doi:10.2174/092986710793348536

Abstract

Increases or decreases in the contractile response of smooth muscle underlie important pathological conditions such as hypertension, incontinence and altered gastrointestinal transit. These disorders are also frequently encountered in the aged population. Oxidative stress and inflammation are key features in the initiation, progression, and clinical manifestations of smooth muscle disorders. Melatonin, the major secretory product of the pineal gland, has free radical scavenging and antioxidative properties and protects against oxidative insult. Recently, widespread interest has grown regarding the apparent protective effects of melatonin on smooth muscle dysfunction. “In vitro” studies have shown that melatonin decreased vascular tone of vascular beds from control, hypertensive or aged animals, through the reduction of adrenergic contraction and the increase in acetylcholine-induced relaxation. “In vivo”, melatonin also attenuates sympathetic tone by direct activation of melatonin receptors, scavenging free radicals or increasing NO availability in the central nervous system. In the gastrointestinal tract, melatonin treatment improves age-related impairments in gallbladder contractility and prevents deleterious effects of cholecystitis on smooth muscle and the enteric nervous system through suppression of oxidative stress. In addition, melatonin improves colonic transit time in constipation-predominant IBS patients. Melatonin is also able to restore impaired contractility of the detrusor muscle from old animals through normalization of Ca2+ dependent and independent contraction, mitochondrial polarity, neuromuscular function and oxidative stress, which would explain the effects of melatonin counteracting cystometric changes in senescent animals. It also reverses bladder damage following ischemia/reperfusion. In conclusion, melatonin may be a promising candidate for future research of agents that modulate smooth muscle motility.

Keywords: Aging, bladder, blood pressure, gut, inflammation, melatonin, smooth muscle, neurotransmitters, depolarization, MLCK, clinical manifestations, dependent contraction, sarcoplasmic reticulum, phosphorylates, suprachiasmatic nuclei, P450 monooxygenases, lipophillicity, immune-modulatory effects, N1-acetyl-N2-formyl-5-methoxykyinuramine (AFMK), endogenous antioxidants (glutathione), reperfusion, myoclonic epilepsy, postprandial decline, anti-atherosclerotic, nocturnal hypertension melatonin, cardiovascular disorders, lipidic peroxidation, xanthine oxidoreductase, reestablishment, spontaneous hypertensive rats, vasoconstriction, vasorelaxant effects, Premotor neurons, postsynaptic alpha1-adrenergic receptors, Gastroesophageal Reflux Disease (GERD), gastric-protection, capsaicin-sensitive relaxant nerves, laparoscopic, inflammatory response, immunological injury, antioxidant properties, bladder innervation, hypocontractility, MYOMETRIUM, cycle/pineal melatonin secretion, adrenoceptors, fibromyalgia, therapeutic arsenal, CBDL, RNS