Blood pressure reducing effects of piromelatine and melatonin in spontaneously hypertensive rats.

摘要

Recently, widespread interest has grown regarding melatonin treatment of hypertension including its cardioprotective effects. Studies in rodents indicate that melatonin plays a role in the pathogenesis of hypertension in rats with metabolic syndrome. Piromelatine, a melatonin agonist, serotonin 5-HT-1A and 5-HT-1D agonist and serotonin 5-HT2B antagonist is a multimodal agent with sleep promoting, anti-diabetic, analgesic, anti-neurodegenerative, anxiolytic and antidepressant potential, currently in development for the treatment of insomnia. In this report we assessed the effects of piromelatine and melatonin treatment on blood pressure in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Five groups of 12-wk-old rats (10/group) were treated for 5 weeks with a vehicle, piromelatine (5, 15 and 50 mg/kg BW) and melatonin (10 mg/kg BW) and an age-matched WKY control group. Systolic blood pressure (tail-cuff method) was measured weekly at 9:00 a.m. and at 9:00 p.m. The rats body weight, plasma glucose, insulin, triglyceride, adiponectin, total cholesterol, HDL and LDL/VLDL cholesterol were also measured. Our results showed that both piromelatine and melatonin reduced SHR blood pressure significantly both during the morning and the evening. Piromelatine, but not melatonin, also reduced SHR body weight gain and both significantly decreased plasma glucose and insulin levels and increased adiponectin levels. Piromelatine, similar to melatonin, has an antihypertensive effect and also attenuates body weight, improves metabolic profiles and might be useful in the treatment of hypertension and the metabolic syndrome.