健常者の運動負荷における心房性ナトリウム利尿ペプチドの血中変動

Clinical evaluation on the response of plasma atrial natriuretic peptide to exercise in healthy volunteers

　心房性ナトリウム利尿ペプチド（ANP）がde Boldら^1）により発見され，さらに松尾ら^2）により単離・同定されて以来，その生理学的および病態生理学的意義の検討^3〜7）が盛んに行われている。最近ではANPが心臓より冠状静脈洞を介して^8），血中に分泌され著明な降圧作用^9）ないしNa利尿作用^10）を持ち，血圧調節ならびに水・電解質調節に関与しているとされている。一方，ANPが分泌亢進する病態としては心不全^5），腎不全^11,12）などの容量負荷病態あるいは高血圧^13），発作性上室性頻拍^14），高食塩食^4）などがあげられている。われわれも心不全^15）および腎不全例^16）でANPが著しい高値を示し，症状ならびに病態の改善とともに減少することを報告した。今回は運動負荷時におけるANPの血中動態を観察し，その分泌機序を健常者を対象として検討した。

To investigate the responce of plasma atrial nat-riuretic peptide (ANP) to exercise in healthy vo-lunteers, we measured the plasma level of ANP, catecholomine, Renin, angiotensin, aldosteron, anti-diuretic hormone and the hemodynamic parameters.

The plasma level of ANP in 11 normal subjects averaged 35.5±6.3 pg/ml under control condition was increased to 60.9±10.8 pg/ml (76.1%, p<0.005) at the endpoint of treadmill exercise (85% of tar-get heart rate) and rapidly fell at the recovery phase. Compared with control value, plasma level of norepinephrine and epinephrine were significan-tly elevated from 157±23.6 to 781±85.2 pg/ml (p<0.005), 39.4±7.1 to 67.7±17 pg/ml (p<0.025) respectively at the endpoint of exercise. And then, plasma concentration of renin activity and antidiu-retic were also significantly increased from 2.15±0.4 to 3.37±0.53 ng/ml/h (p<0.025), 3.18±0.55 to 4.67±0.88 pg/ml (p<0.025), while angiotensin Ⅱ and aldosteron were not significantly different from control (rest) value. Systolic pressure, diastolic pres-sure, heart rate, mean blood pressure and pressure rate product were increased significantly (p<0.005 to p<0.05) at the termination of exercise. Maximal percent increases were +38.2% on average for systolic pressure, +19.2% for diastolic pressure, +20.1% for mean blood pressure, +121% for heart rate and +196% for pressure rate product. There were closely correlation between the maximal per-cent changes of ANP and norepinephrine (r=0.82, p<0.01) or mean blood pressure (r=0.58, p<0.01).

We conclude that the most likely cause for the increased the plasma level of ANP during exercise is increased sympathetic neural activity to the atrium. Further investigation into the mechanisms that regulate ANP secretion in human should inc-lude the sympathetic neural activity.