Daily NO rhythms in peripheral clocks in aging male Wistar rats: protective effects of exogenous melatonin

Sep 12, 2016Biogerontology

Daily nitric oxide patterns in body clocks of aging male rats and protective effects of melatonin

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Abstract

Aging resulted in significant alterations in nitric oxide levels and their daily rhythms in various peripheral organs.

Nitric oxide levels were measured at different times of day in the kidney, intestine, liver, heart, lungs, and testis of male Wistar rats.
Aging was associated with changes in both the levels and the timing of nitric oxide in 12- and 24-month-old rats.
The most significant alterations in nitric oxide daily rhythms were observed in the liver, while the lungs showed the least changes.
Correlation analysis indicated a loss of consistent interactions between the peripheral clocks with aging.
Exogenous melatonin administration was found to differentially restore age-related changes in nitric oxide levels and rhythms in the kidney, intestine, and liver.

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In mammals suprachiasmatic nucleus (SCN), acts as a light entrainable master clock and by generation of temporal oscillations regulates the peripheral organs acting as autonomous clocks resulting in overt behavioral and physiological rhythms. SCN also controls synthesis and release of melatonin (hormonal message for darkness) from pineal. Nitric Oxide (NO) acts as an important neurotransmitter in generating the phase shifts of circadian rhythms and participates in sleep-wake processes, maintenance of vascular tone as well as signalling and regulating inflammatory processes. Aging is associated with disruption of circadian timing system and decline in endogenous melatonin leading to several physiological disorders. Here we report the effect of aging on NO daily rhythms in various peripheral clocks such as kidney, intestine, liver, heart, lungs and testis. NO levels were measured at zeitgeber time (ZT) 0, 6, 12 and 18 in these tissues using Griess assay in male Wistar rats. Aging resulted in alteration of NO levels as well as phase of NO in both 12 and 24 months groups. Correlation analysis demonstrated loss of stoichiometric interaction between the various peripheral clocks with aging. Age induced alterations in NO daily rhythms were found to be most significant in liver and, interestingly least in lungs. Neurohormone melatonin, an endogenous synchroniser and an antiaging agent decreases with aging. We report further differential restoration with exogenous melatonin administration of age induced alterations in NO daily rhythms and mean levels in kidney, intestine and liver and the stoichiometric interactions between the various peripheral clocks.

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Daily NO rhythms in peripheral clocks in aging male Wistar rats: protective effects of exogenous melatonin

Abstract

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