本態性高血圧症におけるレニン・アンジオテンシン系及び交感神経系刺激の血漿ブラジキニン濃度に及ぼす影響

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We studied the possible interplay between plasma bradykinin (P-BK) and the renin-angiotensin axis in essential hypertension, the effect of catecholamine on P-BK by standing and norepinephrine (NE) infusion, and the possible role of bradykinin in the hypotensive mechanism of angiotensin I converting enzyme inhibitor (captopril) in renin-independent essential hypertension. Plasma bradykinin was measured by sensitive radioimmunoassay in 44 hypertensive patients and compared with that of 24 normotensive subjects. P-BK was not significantly reduced in hypertensive patients, and when subjects were divided by age range, the P-BK was reduced by aging in normotensive subjects but not in hypertensive patients, and the elder (60-80 yr) age normotensive group showed significantly (p<0.05) lower P-BK compared with the elder hypertensive aroup. 28 essential hypertensive patients (EHT) who were classified as WHO stagel (n=15) and WHO stagell (n=13) were given 80 mg of furosemide orally and kept upright for 4 hours. Plasma renin activity (PRA), P-BK, plasma aldosterone (P-Ald) and serum angiotensin converting enzyme activity (ACEA) were measured before and after furosemide administration. Twelve normotensive subjects served as controls. PRA, P-Ald and ACEA showed a significant increase (p<0.05) in all groups in response to furosemide. In normotensives, basal P-BK was 11.1 ± 1.3 pg/ml which increased to 15.6 ± 1.8 pg/ml (p<0.02) after furosemide. These changes of P-BK were in parallel with PRA, P-Ald and ACEA. In the WHO stagel EHT group, baseline P-BK was 9.7 ± 1.3 pg/ml which increased to 15.6 ± 1.8 pg/ml (p<0.02) and PRA, P-Ald and ACEA showed a similar increase as in normotensives. In the WHO stagell EHT patients, however, P-BK showed only a slight increase from 9.8 ± 1.0 pg/ml to 12.0 ± 1.1 pg/ml after furosemide. These changes were smaller either than normotensives or the WHO stagel EHT group. There was a slight but significant correlation between PRA and P-BK in normotensives and in the WHO stagel EHT. There was no correlation between PRA and P-BK in the WHO stagell EHT. The present results do not support the view that there may be a direct linkage between the kallikrein kinin system and the renin angiotensin axis mediated by kininase II or angiotensin converting enzyme in human peripheral blood. A blunted response of P-BK in WHO stage II EHT may suggest a secondary alteration of kinin metabolism in the development of hypertension. Plasma norepinephrine (P-NE), P-BK and PRA were measured before and after 10 minutes standing, NE infusion (100 ng/kg/min) for 60 minutes in 10 normotensive subjects. Basal steady state P-NE (135 ± 12 pg/ml) rose to 279 ± 21 pg/ml and PRA also rose, but P-BK did not. Norepinephrine infusion increased P-BK from 13.3 ± 2.6 pg/ml basal to 22.3 ± 2.8 pg/ml (p<0.05) but did not increase PRA. This suggests that at the high extreme of the physiologic range (about 20-fold increase over supine basal), circulating NE caused a major change of P-BK. The effects of a single administration of 100 mg captopril on P-BK in 34 EHT who showed agonistic responses to 1 Sar, 8Ile-angiotensin II were studied. When the patients were analysed according to mean blood pressure (MBP) response, the responders showed a significantly greater P-BK increment (p<0.05), whereas the nonresponders did not show such an increase. There was a positive correlation between P-BK increment and the MBP reduction after captopril in EHT. ACEA, P-Ald, P-NE and plasma epinephrine showed no significant changes between responder and nonresponder groups. The present results suggest that bradykinin may be involved in the hypotensive action of captopril in the EHT sub-groups, where the renin angiotensin system appears to play an inert role for the elevation of blood pressure.

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武田仁勇
金沢大学医学部内科学第二講座

本態性高血圧症におけるレニン・アンジオテンシン系及び交感神経系刺激の血漿ブラジキニン濃度に及ぼす影響

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