Hexarelin Research On The Protective Effect And Mechanism Of The Cardiovascular System

Synthetic growth hormone releasing peptides possess strong growth hormone-releasing effects and effusive peripheral activities. Recently, several independent observations indicated that GHRP exerts cardiovascular activities. We investigated the effects of hexarelin on cardiomyocyte apoptosis in rats with heart failure, cardiac hypertrophy and atherosclerosis in in vivo and in vitro models. At first, the effects of hexarelin on cardiomyocyte apoptosis induced by Ang II, and effects of four GHRPs (GHRP-1, GHRP-2, GHRP-6, hexarelin) on cardiomyocyte apoptosis in pressure-over load heart failure rat model were observed in part I and part II. The results showed that (1) hexarelin inhibited cardiomyocyte apoptosis induced by AngII; (2) GHRPs improved cardiac dysfunction and inhibit the cardiomyocyte apoptosis in rats with heart failure. These results indicated that hexarelin abates cardiomyocytes from Ang II-and heart failure-induced cardiomyocyte apoptosis in rat. The possible mechanisms were possibly via inhibiting the activity of caspase-3, inhibiting bax mRNA expression, increasing the expression of bcl-2 mRNA and inhibiting the expression of p38MAPK protein. (3) Hexarelin inhibited cardiomyocyte hypertrophy induced by Ang II and inhibit the cardiac hypertrophy of SHR. The mechanisms of the antihypertrophy effect of hexarelin may be associated with inhibition of ATI receptor mRNA expression, with upregulation of the expression of AT2 receptor mRNA and ERK1/2 activity. As hexarelin could affect the renin-angiotensin system, with the inhibition of hexarelin may have effect on the development of atherosclerosis. We investigated the effect of hexarelin on the astherosclerosis model of rat and the effect of hexarelin on proliferation of vascular smooth muscle cell(VSMC) induced by Ang II. (4) Hexarelin showed obvious antiatheosclerosis effects. The underlying mechanisms may related with the increasing of serum HDL-c and NO, the decreasing of serum LDL-c, the attenuate of accumulation of lipid and calcium deposits in aorta and the inhibition of VSMC proliferation induced by Ang II. These effects of GHRP may be also associated with the upregulation of CD36 mRNA. Taken together, administration of...