一氧化氮與自主神經系統參與Fg Bbeta_15-42胜肽之抗高血壓作用

Participation of Nitric Oxide and Autonomic Nervous System in the Antihypertensive Effect of Fg Bbeta_15-42 Peptides

本研究探討Fg Bbeta_15-42胜肽參與心血管活性作用及其作用機轉。以自發性高血壓大鼠進行心血管活性試驗，發現Fg Bbeta_15-42胜肽（0.25, 0.5 及1 mg／kg, i.v.）具有明顯劑量相關性降低動脈血壓、心跳速率、心臟收縮力及交感神經性血管運動張力。也發現胜肽所產生顯著降低交感神經性血管運動張力之作用，與降低動脈血壓反應間具有時間正相關性。反之，對照組實驗發現以相同體積生理食鹽水及熱破壞之胜肽（1 mg／kg, 60°C, 15分鐘）注射後，對這些心血管參數卻無顯著影響。在高血壓大鼠的機轉研究中，發現該胜肽（0.5 mg／kg, i.v.）之心血管抑制作用是明顯受hexamethonium（30 mg／kg）、N^G-nitro-L-arginine methyl ester（20 mg／kg）或N5-（1-Iminoethyl）-L-ornithine（5 mg／kg）的預前處理所拮抗。這些結果顯示Fg Bbeta_15-42胜肽具有顯著抗高血壓作用，其機轉可能與阻斷交感神經性血管運動張力及調節血管內皮性一氧化氮形成有關。

This study explored that the role of Fg Bbeta_15-42(15-42) peptide in cardiovascular activity and its mechanism of action. The cardiovascular activity test was conducted on spontaneously hypertensive rats and it was found that Fg Bbeta_15-42(15-42) peptide (0.25, 0.5 and 1 mg/kg, i.v.) had a significant dose-dependent reduction in arterial blood pressure, heart rate, cardiac contractility and sympathetic vasomotor tone. It was also found that the effect of peptides on significantly reducing sympathetic vasomotor tone has a positive time correlation with the reduction of arterial blood pressure response. In contrast, the control group experiment found that the same volume of normal saline and heat-inactivated peptide (1 mg/kg, 60°C, 15 min) had no discernible effect on these baseline cardiovascular parameters. In the mechanism study of hypertensive rats, it was found that the cardiovascular depressive effects of this peptide (0.5 mg/kg, i.v.) were significantly blocked by pretreatment with hexamethonium (30 mg/kg), N^G-nitro-L-arginine methyl ester (20 mg/kg), or N5-(1-Iminoethyl)-L-ornithine (5 mg/kg). Together these results demonstrate that Fg Bbeta_15-42(15-42) peptide has a significant antihypertensive effect, and its mechanism might be mediated through the withdrawal of sympathetic vasomotor tone and nitric oxide generated by vascular endothelium.