Hypertension and Cardiovascular Remodelling in Rats Exposed to Continuous Light: Protection by ACE-Inhibition and Melatonin

Abstract

Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day) exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old male Wistar rats (10 per group) were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100 mg/kg/day) or melatonin (10 mg/kg/day). Exposure to continuous light led to hypertension, left ventricular (LV) hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LV hypertrophy development and only melatonin reduced LV hydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease.

Melatonin: the dawning of a treatment for fibrosis?

“…During the development of pathological fibrosis, ECM components, including collagen and GAG, acuumelate in excess. Melatonin contributes to a reduction in the amount of collagen and GAG , and finally contributes to the histopathological improvement . In summary, melatonin impacts every stage during the process of anti‐fibrosis (Fig.…”

“…In many disease states, fibrosis is initiated by the inflammation and oxidative stress. Fibrosis inhibition always accompanies a reduction in the inflammatory response caused by melatonin , as well as following a reduction in oxidative stress . The mechanism of GAG content reduction cannot be explained by a direct action of the pineal indoleamine on myofibroblasts during the healing of a myocardial infarction site, indicating the changes in GAG may be an indirect action of melatonin, which may be a result of modulating inflammation at the area of infarction .…”

“…Previous studies have demonstrated the accumulation of fibrosis in numerous conditions. Melatonin is typically involved in the prevention or elimination of fibrosis, including after myocardial infarction , pulmonary hypertension , spontaneously hypertension , isoproterenol‐induced rebuilding , light and N ‐nitro‐ l ‐arginine‐methyl ester ( l ‐NAME) treatment , obstructive sleep apnea (OSA) , radiation , and chronic Trypanosoma cruzi infection . Moreover, in vivo melatonin also prevents the accumulation of collagen I and augmentation of fibrotic markers, TGF‐β and CTGF, in cardiac myofibroblasts induced by leptin .…”

Role of melatonin in blood pressure regulation: An adjunct anti‐hypertensive agent

“…Finally, in a direct comparison of melatonin and captopril, an ACE‐inhibitor, melatonin ameliorated the increase in systolic blood pressure induced via continuous light exposure. Furthermore, while captopril reduced left ventricular hypertrophy, only melatonin reduced left ventricular fibrosis in the light‐induced hypertensive model …”

Peripheral and Central Effects of Melatonin on Blood Pressure Regulation

“…Thirdly, in the agreement with the proven melatonin deficiency in certain types of hypertension, the supplementation of pinealectomized or continuous light-exposed animals with melatonin prevented hypertension development [120]. In the clinical setting, several weeks of melatonin administration before sleep reduced nocturnal systolic and diastolic BP in non-dipping untreated patients [113], in non-dipping women [87] and in patients with nocturnal hypertension [121].…”