Effects of a single dose of captopril on blood pressure and the renin-angiotensin-aldosterone system in normal subjects and hypertensive patients with various etiologies

Effect of a single dose of captopril on blood pressure and the renin-angiotensin-aldosterone (R-A-A) system was evaluated in 0 normal subjects and 11 hypertensive patients with various etiologies. Captopril was administered orally to normal healthy subjects and hypertensive patients on unrestricted...

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Published inNihon Jinzo Gakkai shi Vol. 21; no. 11; pp. 1185 - 1192
Main Authors Kumahara, Yuichi, Higaki, Jitsuo, Maruyama, Anna, Takeshi, Hata, Mikami, Hiroshi, Naka, Toru, Ogihara, Toshio, Kanda, Takao, Gotoh, Motoki
Format Journal Article
LanguageJapanese
Published Japan Japanese Society of Nephrology 01.11.1979
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ISSN0385-2385
1884-0728
DOI10.14842/jpnjnephrol1959.21.11_1185

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Abstract Effect of a single dose of captopril on blood pressure and the renin-angiotensin-aldosterone (R-A-A) system was evaluated in 0 normal subjects and 11 hypertensive patients with various etiologies. Captopril was administered orally to normal healthy subjects and hypertensive patients on unrestricted diet. Blood pressure was monitored for 4 hours. Blood was drawn at 0, 30 min., 1, 2, 3 and 4 hours for analysis of plasma renin activity (PRA), angiotensin I concentration (AI) and aldosterone concentration (PAC). Angiotensin II analogue (AIIA) test was done in each sub-jects after sodium depletion (40 mg f urosemide administration daily and mild sodium restricted diet for 3 days) Captopril in a dose of 100 mg caused no blood pressure change, increased PRA, AI and decreased PAC in normal subjects. When captopril was administered to patients with renovascular or malig-nant hypertension, blood pressure fell significantly for 4 hours, PRA and Al increased and PAC decreased for 4 hours. In low reninemic patients these paramenters showed little change. In all the subjects studied, change in mean blood pressure was inversely correlated with pre-treatment PRA value (y=-1.4×-2.8, r=0.85, p>0.001). Magnitude of blood pressure reduction by captopril was significantly correlated with that induced by angiotensin II antagonist (y=0.8×-5.0, r=0.93, p>0.001). From the results obtained, it is concluded that the acute blood pressure lowering effect of captopril in hyperreninemic hypertensive patients closely related to its effect on the suppression of R-A-A system. It may be useful to monitor the acute phase response of captopril to provide a prediction for the effectiveness of long term treatment of hypertension.
AbstractList Effect of a single dose of captopril on blood pressure and the renin-angiotensin-aldosterone (R-A-A) system was evaluated in 0 normal subjects and 11 hypertensive patients with various etiologies. Captopril was administered orally to normal healthy subjects and hypertensive patients on unrestricted diet. Blood pressure was monitored for 4 hours. Blood was drawn at 0, 30 min., 1, 2, 3 and 4 hours for analysis of plasma renin activity (PRA), angiotensin I concentration (AI) and aldosterone concentration (PAC). Angiotensin II analogue (AIIA) test was done in each sub-jects after sodium depletion (40 mg f urosemide administration daily and mild sodium restricted diet for 3 days) Captopril in a dose of 100 mg caused no blood pressure change, increased PRA, AI and decreased PAC in normal subjects. When captopril was administered to patients with renovascular or malig-nant hypertension, blood pressure fell significantly for 4 hours, PRA and Al increased and PAC decreased for 4 hours. In low reninemic patients these paramenters showed little change. In all the subjects studied, change in mean blood pressure was inversely correlated with pre-treatment PRA value (y=-1.4×-2.8, r=0.85, p>0.001). Magnitude of blood pressure reduction by captopril was significantly correlated with that induced by angiotensin II antagonist (y=0.8×-5.0, r=0.93, p>0.001). From the results obtained, it is concluded that the acute blood pressure lowering effect of captopril in hyperreninemic hypertensive patients closely related to its effect on the suppression of R-A-A system. It may be useful to monitor the acute phase response of captopril to provide a prediction for the effectiveness of long term treatment of hypertension.
Author Gotoh, Motoki
Maruyama, Anna
Naka, Toru
Higaki, Jitsuo
Kumahara, Yuichi
Takeshi, Hata
Ogihara, Toshio
Kanda, Takao
Mikami, Hiroshi
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References 4) Gavras, H., Brunner, H. R., Turini, G.A., Kershaw, G. R., Tuft, C. P., Cuttelod, S., Gavras, I., Vukovich, R. A. & Mckinstry, D. N.: Antihypertensive effect of the oral angiotensin coverting enzyme inhibitor SQ 14225 in man. N. Engl. J. Med. 298: 991-995, 1978.
12) 荻原俊男,三上洋,円山アンナ,中透,桧垣実男,波多丈,中丸光昭,万代隆,神田敬夫,熊原雄一:レニン・アンジオテンシン系抑制剤総合臨牀28:316-322×979.
1) Ondetti,M. A., Rubin, B. & Cushman, D, W. Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents. Science 196: 441-444, 1977.
9) Erdos, E. G. : Angiotensin I converting enzyme. Cir. Res. 36-247-255, 1975.10) Brunner, H. R., Waeber, B., Wauters, J. P., Turini, G., Mckinstry, D. & Gavras H,: In-nappropriate reamn secretion unmarked by captopril (SQ 14,225) in hypertension of chronic renal failure. Lancet 2 m 704-707, 1978.
11) Case, D. B., Atlas, S. A., Laragh, J. H., Sealey, J. E., Sullivan, P. A. & Mckinstry, D. N.: Clinical experience with blockade of the renin-angiotensin-aldosterone system by an oral convertingenzyme inhibitor (SQ 14,225, captpril) in hypertension patients. Progr. Cardiovasc. Dis. 21: 195-206, 1978.
15) Maruyama, A. & Ogihara, T. (in preparation
7) Ogihara, T., Yamameto, T., Doi, K., Omori, K. & Kumahara, Y. m Angiotensin I radioim-munoassay and its application for measurement of plasma reamn activity. Jpn. J. Nuci. Med. 10: 555-563, 1973. (In Japanese.
3) Bravo, E. L. & Tarazi, R. C,: Efficacy of ann orally-active converting enzyme inhibitor (SQ 14, 225) in the treatment of renovascular hypertension (RVH) in man. Kidney Int. 12 497, 1977.
6) Ogihara, T., Hata, T., Mikami, H., Nakamaru, M., Maruyama, A., Mandai, T. & Kumahara, Y.: Sodium depletion and blood pressure response to 1-sarcosine, 8-isoleucine angiotensin II in hypertension. Clin. Pharmacol. Ther. 23 566-572, 1978.
14) Case, D. B., Wallace, J. M,, Keim, H. J,, Weber, M., Sealy, J. & Laragh, J. H. : Possible role role of renin in hypertension as suggested by rm enin-sodium profiling and inhibition of converting enzyme, N. Engl. JB Med. 296 641 646, 1977.
2) Ferguson, R. K., Brunner, H. R., Turini, G.A., Gavras, H. & Mckinstry, D.N.: A specific orally active inhibitor of angiotensin-conver-ting enzyme in man. Lancet 1: 775-778, 1977.
8) Ogihara, T., Iinuma, K., Nishi, K., Arakawa, Y., Takagi, A., Kurata, K., Miyai, K. & Ku. mahara, Y.: A non-chromatographic non-extraction radioimmunoassay for serum aldos-terone. J. Clin. Endocrinol. Metab. 45: 736- 731, 1977.
13) Marks, A. D., Marks, D. B., Kanefsky, T. M., Adlin, V. E. & Channick, B. J. Enhanced adrenal responsiveness to angiotensin II in patients with low renin essential hypertension J. Clin. Endocrinol. Metab. 48. 266-270, 1979.
5) Brunner, H. R., Gavras, H., Waeber, B., Kershaw, G. R., Turini, G. A., Vukovich, R. A. & Mckinstry, D. N.: Oral angiotensin-conver-ting enzyme inhibitor in long-term treatment of hypertensive patients. Ann. Int. Med. 90: 19-23, 1979.
References_xml – reference: 14) Case, D. B., Wallace, J. M,, Keim, H. J,, Weber, M., Sealy, J. & Laragh, J. H. : Possible role role of renin in hypertension as suggested by rm enin-sodium profiling and inhibition of converting enzyme, N. Engl. JB Med. 296 641 646, 1977.
– reference: 15) Maruyama, A. & Ogihara, T. (in preparation)
– reference: 1) Ondetti,M. A., Rubin, B. & Cushman, D, W. Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents. Science 196: 441-444, 1977.
– reference: 9) Erdos, E. G. : Angiotensin I converting enzyme. Cir. Res. 36-247-255, 1975.10) Brunner, H. R., Waeber, B., Wauters, J. P., Turini, G., Mckinstry, D. & Gavras H,: In-nappropriate reamn secretion unmarked by captopril (SQ 14,225) in hypertension of chronic renal failure. Lancet 2 m 704-707, 1978.
– reference: 13) Marks, A. D., Marks, D. B., Kanefsky, T. M., Adlin, V. E. & Channick, B. J. Enhanced adrenal responsiveness to angiotensin II in patients with low renin essential hypertension J. Clin. Endocrinol. Metab. 48. 266-270, 1979.
– reference: 5) Brunner, H. R., Gavras, H., Waeber, B., Kershaw, G. R., Turini, G. A., Vukovich, R. A. & Mckinstry, D. N.: Oral angiotensin-conver-ting enzyme inhibitor in long-term treatment of hypertensive patients. Ann. Int. Med. 90: 19-23, 1979.
– reference: 7) Ogihara, T., Yamameto, T., Doi, K., Omori, K. & Kumahara, Y. m Angiotensin I radioim-munoassay and its application for measurement of plasma reamn activity. Jpn. J. Nuci. Med. 10: 555-563, 1973. (In Japanese.)
– reference: 6) Ogihara, T., Hata, T., Mikami, H., Nakamaru, M., Maruyama, A., Mandai, T. & Kumahara, Y.: Sodium depletion and blood pressure response to 1-sarcosine, 8-isoleucine angiotensin II in hypertension. Clin. Pharmacol. Ther. 23 566-572, 1978.
– reference: 11) Case, D. B., Atlas, S. A., Laragh, J. H., Sealey, J. E., Sullivan, P. A. & Mckinstry, D. N.: Clinical experience with blockade of the renin-angiotensin-aldosterone system by an oral convertingenzyme inhibitor (SQ 14,225, captpril) in hypertension patients. Progr. Cardiovasc. Dis. 21: 195-206, 1978.
– reference: 3) Bravo, E. L. & Tarazi, R. C,: Efficacy of ann orally-active converting enzyme inhibitor (SQ 14, 225) in the treatment of renovascular hypertension (RVH) in man. Kidney Int. 12 497, 1977.
– reference: 12) 荻原俊男,三上洋,円山アンナ,中透,桧垣実男,波多丈,中丸光昭,万代隆,神田敬夫,熊原雄一:レニン・アンジオテンシン系抑制剤総合臨牀28:316-322×979.
– reference: 2) Ferguson, R. K., Brunner, H. R., Turini, G.A., Gavras, H. & Mckinstry, D.N.: A specific orally active inhibitor of angiotensin-conver-ting enzyme in man. Lancet 1: 775-778, 1977.
– reference: 8) Ogihara, T., Iinuma, K., Nishi, K., Arakawa, Y., Takagi, A., Kurata, K., Miyai, K. & Ku. mahara, Y.: A non-chromatographic non-extraction radioimmunoassay for serum aldos-terone. J. Clin. Endocrinol. Metab. 45: 736- 731, 1977.
– reference: 4) Gavras, H., Brunner, H. R., Turini, G.A., Kershaw, G. R., Tuft, C. P., Cuttelod, S., Gavras, I., Vukovich, R. A. & Mckinstry, D. N.: Antihypertensive effect of the oral angiotensin coverting enzyme inhibitor SQ 14225 in man. N. Engl. J. Med. 298: 991-995, 1978.
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SubjectTerms Adult
Aldosterone - blood
Angiotensin I - blood
Angiotensins - blood
Blood Pressure - drug effects
Captopril - administration & dosage
Captopril - pharmacology
Humans
Hypertension - physiopathology
Male
Proline - analogs & derivatives
Renin - blood
Title Effects of a single dose of captopril on blood pressure and the renin-angiotensin-aldosterone system in normal subjects and hypertensive patients with various etiologies
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