本態性高血圧症における血清アンジオテンシンI変換酵素の動態に関する研究
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The present study was designed to clarify the role of serum angiotensin I-converting enzyme (ACE) in the occurrence and maintenance of hypertension in essential hypertension (EH). For this purpose, following experiments were carried out : 1) Correlations between serum ACE activity and renin activity (PRA), aldosterone concentration (PAC) and bradykinin concentration (PBC) in plasma, and blood pressure (BP) as well as serum creatinine levels. 2) Circadian rhythm of serum ACE activity, and 3) Effect of furosemide, upright posture, both furosemide and upright posture, propranolol, indomethacin, 9α-fluorocortisol or angiotensin II (A-II) on the serum ACE activity, PRA, PAC and circulating plasma volume (CPV).<BR>The following results were obtained : <BR>1) The serum ACE activity was 30.2 ±5.0 U/ml (means ±SD) in EH as a group, which was significantly higher than that (27.3 ± 3.9 U/ml) in age matched normotensive subjects (NT) (p<0.001). While there was no significant difference in the enzyme activity between low-renin EH (LREH) and NT, a significant difference was found between normal- (NREH) or high-renin EH (NREH) and NT (p<0.05 for NREH, p<0.01 for HREH).<BR>2) A negative correlation was observed between enzyme activity and age in EH (r=-0.221, 0.05<p<0.10) as well as in NT (r=-0.306, p<0.05).<BR>3) No significant relationships were observed between enzyme activity and BP in either EH or NT.<BR>4) There was a significant positive correlation between enzyme activity and PRA in NT (r=0.501, p<0.001), NREH (r=0.658, p<0.001) and HREH (r=0.695, p<0.001). However, no significant relationship was found between them in LREH. The enzyme activity was significantly correlated to PAC in NT (r=0.368, p<0.01), NREH (r=0.567, p<0.001) and HREH (r= 0.529, p<0.01), but not in LREH. Although no significant correlation was observed between enzyme activity and PBC in NT, NREH and HREH, a significant relationship was found in LREH (r=-0.460, 0.05<p<0.10).<BR>5) The enzyme activity was not related to serum creatinine levels in EH as well as in NT.<BR>6) In NT, the serum levels of ACE activity reached a maximum values at 6 : 00 a.m. or 9 : 00 a.m., and gradually decreased between 6 : 00 p.m. and 3 : 00 a.m. An almsot similar circadian rhythm of enzyme activity was found in EH. The rhythm was parallel that of PRA and PAC in NT, NREH and HREH, but not in LREH.<BR>7) The serum ACE activity was significantly increased by treatments with furosemide, upright posture and both furosemide and upright posture in NREH and HREH as well as NT, parallel with changes in PRA in response to these types of stimulations. On the other hand, serum ACE activity was lowered by treatments with propranolol, indomethacin, 9α-fluorocortisol or A-II, also in parallel with changes in PRA. However, in LREH, serum ACE activity was not changed with upright posture and propranolol, but it was changed with furosemide, 9α-fluorocortisol or indomethacin in parallel with change of CPV.<BR>In conclusion, the ACE may be secreted into circulation from the kidney in response to renin release and be activated the renin-angiotensin-aldosterone (R-A-A) axis in NREH and HREH as well as in NT. On the other hand, in LREH, serum ACE may be inactivated the kallikrein-kinin system rather than that the R-A-A axis and be modulated BP and water-electrolyte balance.
- 一般社団法人 日本内分泌学会の論文
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