The Role of Melatonin In Exercise Enhanced Endothelium-dependent Vasorelaxation In Mesenteric Arteries of SHR

Abstract

PURPOSE: To determine if melatonin plays an important role in the hypotensive effects of exercise training. Further, to study the role of melatonin binding to melatonergic receptors in the vasorelaxation of small MAs in SHR. METHODS: Twelve-week-old male normotensive Wistar-Kyoto rats (WKY, n=18) and SHRs (n = 48) were used. SHRs were randomly divided into four groups: SHR sedentary group (SHR-SED, n = 18), SHR sedentary with melatonin receptor antagonist luzindole (Luz) injection group (SHR-SED + Luz, n = 6), SHR exercise group (SHR- EX, n = 18) , and SHR exercise with luzindole injection group (SHR-EX + Luz, n = 6). Luzindole injection groups were injected intraperitoneally (i.p.) with luzindole (1 mg/ kg/day in sterile saline) each day. Rats in the exercise groups were subjected to aerobic exercise. Blood pressure and heart rate were measured after exercise. Serum melatonin levels were examined by ELISA. The mechanical properties of small mesenteric arteries were studied with myograph. Western blot and immunofluorescence colocalization were performed to examine the protein expression and distribution of MT1, MT2 receptors and eNOS. RESULTS: Exercise training produced a significant reduction in blood pressure and heart rate in SHR, which was significantly attenuated by intraperitoneal administration of luzindole, a nonselective melatonin receptor (MT1/MT2) antagonist. Serum melatonin levels in the SHR group were significantly lower than those in the WKY group at 8:00-9:00 and 21:00-22:00, and exercise training reduced this difference. Endothelium-dependent vessel relaxation induced by acetylcholine was significantly blunted in SHR compared with age-matched WKY. Both exercise training and luzindole ameliorated this endothelium-dependent impairment of relaxation in hypertension. Immunohistochemistry and Western blotting showed that protein expression of the MT2 receptor and eNOS, as well as their colocalization in the endothelial cell layer in SHR, was significantly decreased; exercise training suppressed this reduction. CONCLUSIONS: These results provide evidence that regular exercise has a beneficial effect on improving endothelium-dependent vasorelaxation in MAs, in which melatonin plays a critical role by acting on MT2 receptor to increase NO production and/or NO bioavailability.