Ramelteon attenuates age-associated hypertension and weight gain in spontaneously hypertensive rats
The neuroendocrine theory of aging suggests the common mechanisms of developmental (prereproductive) and aging (postreproductive) processes and identified a cluster of conditions (hypertension, obesity, dyslipidemia, type 2 diabetes, menopause, late onset depression, vascular cognitive impairment, impairment of immune defense, and some forms of cancer) as age-associated neuroendocrine disorders (AAND). Obesity, dyslipidemia, hypertension, and type 2 diabetes were later described as metabolic syndrome (MetS). Because melatonin attenuated development of MetS is age-dependent, that is, in young and old, but not in middle-aged rats, we studied the effect of the selective melatonin agonist, Ramelteon, on the two core symptoms of MetS/AAND: hypertension and body weight gain in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto male rats (WKY). SHR rats developed hypertension at the time of maximal weight gain that coincided with the onset of reproductive activity (810 weeks old). Chronic (but not acute) administration of Ramelteon (in drinking water, 8 mg/kg/day, from 4 to 12 weeks of age) attenuated age-associated increase of systolic blood pressure (tail-cuff method) by 45%, and age-associated body weight gain by 30%. Acute and chronic Ramelteon did not affect blood pressure and body weight in normotensive WKY rats. Ramelteon-induced attenuation of age-associated hypertension and weight gain suggests that Ramelteon might attenuate the other symptoms of MetS/AAND and might be useful in the treatment of MetS/AAND during puberty, menopause, and old age.
ramelteon aging aging hypertension weight gain spontaneously hypertensive rats age-associated neuroendocrine disorders metabolic syndrome melatonin age