Ramelteon attenuates age-associated hypertension and weight gain in spontaneously hypertensive rats

Ann N Y Acad Sci. 2010 Jun;1199:114-20. doi: 10.1111/j.1749-6632.2009.05355.x.


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 (8-10 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Indenes / pharmacology
  • Indenes / therapeutic use*
  • Male
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Weight Gain / drug effects*


  • Indenes
  • ramelteon