Circadian Variations of Total Renin, Active Renin, Plasma Renin Activity and Plasma Aldosterone in Clinically Healthy Young Subjects
Summary The direct assay of total renin (TRC) and active renin concentration (ARC) is a reality due to the availability of monoclonal antibodies against human renin. Because of this, a study has been performed in order to assess the circadian rhythmicity of TRC and ARC. The study was extended to plasma renin activity (PRA) and plasma aldosterone concentration (PAC) for a more complete assessment of the renin-angiotensin-aldosterone system (RAAS). Twelve clinically healthy subjects (6 males and 6 females, age from 20 to 25 years) volunteered for this study. Timequalified data series were analysed by means of chronobiological procedures in order to validate the circadian rhythm and to correlate the sinusoidal profiles. The circadian rhythm was validated at a high significance for TRC, ARC, PRA and at a borderline significance for PAC. The periodic oscillations were significantly correlated, demonstrating that TRC, ARC, PRA and PAC cycles oscillate in synchronism during the 24-hour span. Key words Circadian Rhythm — Total Renin Concentration — Active Renin Concentration — Renin-AngiotensinAldosterone System — Cosinor Analysis
Introduction
The circadian rhythmicity also attains to prorenin, the precursor of active renin {Cugini, Salandi, Murano, Centanni and Scavo 1983). In the recent past, the determination of circulating prorenin was carried out via an indirect estimate according to the technique called cryoactivation {Sealey, Moon, Laragh and Alderman 1976). Renin, in turn, was measured as an enzymatic activity, its direct assay via antirenin monoclonal antibodies being not yet available. Presently, the direct measurement of both total renin and active renin becomes available using immunoassay technique {Galen, Guyenne, Devaux, Auzan, Corvol and Menard 1979; Galen, Devaux, Atlas, Guyenne, Menard, Corvol, Simon, Cazaubon, Richer, Badouaille, Richaud, Gros and Pau 1984; Guyenne, Galen, Devaux, Corvol and Menard 1980; Yokosawa, Yokosawa and Inagami 1980; Dzau, MudgettHunter, Kapler and Haber 1981; Pau, Simon, Galen, Devaux, Soubrier, Menard and Corvol 1981; Simon, Galen, Devaux, Soubrier, Pau, Menard and Corvol 1981; Menard, Guyenne, Corvol, Pau, Simon and Roncucci 1985; Dessi-Fulgheri, Cocco, Glorioso, Bandiera, Madeddu and Rappelli 1987; Morganti, Turolo, Pulazzini and Zanchetti 1987). This prompts the present study on the circadian periodicity of human renins with the aim of better investigating the physiology of RAAS. Materials and Methods Subjects and Protocol Twelve clinically healthy young subjects gave their informed consent to be studied. They were 6 men and 6 women ranging in age from 22 to 25 years. They were found to be healthy by an extensive clinical checkup.
Several investigations demonstrated that the renin-angiotensin-aldosterone system (RAAS) is constituted by biochemical variables that oscillate in human blood with a circadian periodicity {Gordon, Wolfe, Island and Liddle 1966; Vagnucci, McDonald, Drash and Wong 1974; Armbruster, Vetter, Beckerhoff, Nussberger and Vetter 1975; Katz, Romph and Smith 1975; Modlinger, Sharif-Zadeck, Ertel and Gutkin 1976; Cugini, Manconi, Serdoz, Mancini, Meucci and Scavo 1980; Kawasaki, Ueno, Uezono, Matsuoka, Omae, Halberg, Wendt, Taggett-Anderson and Haus 1980; Kawasaki, Uezono, Ueno, Omae, Matsuoka, Haus and Halberg 1983).
Each subject was investigated under controlled conditions of sodium (Na) and potassium (K) intake. The electrolyte balance was assessed by the urinary Na and K excretion rate (urinary Na: 175 + 16 mEq/day, urinary K: 35.5 ±2.5 mEq/day). Determinations of total renin concentration (TRC), active renin concentration (ARC), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were carried out in systemic venous blood drawn 8 times over a period of 25 hours starting at 0800. While the first blood sampling was done with subjects in sitting position and was utilized for a control of normalcy, the subsequent specimens were taken from 1200 to 0800 in subjects who were recumbent in horizontal position 1 hour prior to each blood collection. The last sampling at 0900 was done with
Horm.metab.Res.22(1990)636-639 © Georg Thieme Verlag Stuttgart • New York
Received: 3 Aug. 1989
Accepted: 3 May 1990
Downloaded by: National University of Singapore. Copyrighted material.
T. Kawasaki1, P. Cugini, K. Uezono , H. Sasaki1, K. Itoh3, M. Nishiura4 and K. Shinkawa4 Institute of Health Science, Kyushu University, Kasuga, Japan Endocrine Pathophysiology, University of Rome "La Sapienza", Rome, Italy Nakamura Gakuen College, Fukuoka, Japan 4Daiichi Radioisotope Laboratories Ltd., Tokyo, Japan
Horm. metab. Res. 22 (1990)
Circadian Rhythm of Total and Active Renin
Fig. 1 The model of cosinor analysis.
Degrees (360° = 24 h) no
_go°
-180°
-270°
-360° 1 1 1 1 1 1 1
Acrophase (0)
20 18
95 % confidence limits •
«, 16 E 14
Residual
•2
Summary The direct assay of total renin (TRC) and active renin concentration (ARC) is a reality due to the availability of monoclonal antibodies against human renin. Because of this, a study has been performed in order to assess the circadian rhythmicity of TRC and ARC. The study was extended to plasma renin activity (PRA) and plasma aldosterone concentration (PAC) for a more complete assessment of the renin-angiotensin-aldosterone system (RAAS). Twelve clinically healthy subjects (6 males and 6 females, age from 20 to 25 years) volunteered for this study. Timequalified data series were analysed by means of chronobiological procedures in order to validate the circadian rhythm and to correlate the sinusoidal profiles. The circadian rhythm was validated at a high significance for TRC, ARC, PRA and at a borderline significance for PAC. The periodic oscillations were significantly correlated, demonstrating that TRC, ARC, PRA and PAC cycles oscillate in synchronism during the 24-hour span. Key words Circadian Rhythm — Total Renin Concentration — Active Renin Concentration — Renin-AngiotensinAldosterone System — Cosinor Analysis
Introduction
The circadian rhythmicity also attains to prorenin, the precursor of active renin {Cugini, Salandi, Murano, Centanni and Scavo 1983). In the recent past, the determination of circulating prorenin was carried out via an indirect estimate according to the technique called cryoactivation {Sealey, Moon, Laragh and Alderman 1976). Renin, in turn, was measured as an enzymatic activity, its direct assay via antirenin monoclonal antibodies being not yet available. Presently, the direct measurement of both total renin and active renin becomes available using immunoassay technique {Galen, Guyenne, Devaux, Auzan, Corvol and Menard 1979; Galen, Devaux, Atlas, Guyenne, Menard, Corvol, Simon, Cazaubon, Richer, Badouaille, Richaud, Gros and Pau 1984; Guyenne, Galen, Devaux, Corvol and Menard 1980; Yokosawa, Yokosawa and Inagami 1980; Dzau, MudgettHunter, Kapler and Haber 1981; Pau, Simon, Galen, Devaux, Soubrier, Menard and Corvol 1981; Simon, Galen, Devaux, Soubrier, Pau, Menard and Corvol 1981; Menard, Guyenne, Corvol, Pau, Simon and Roncucci 1985; Dessi-Fulgheri, Cocco, Glorioso, Bandiera, Madeddu and Rappelli 1987; Morganti, Turolo, Pulazzini and Zanchetti 1987). This prompts the present study on the circadian periodicity of human renins with the aim of better investigating the physiology of RAAS. Materials and Methods Subjects and Protocol Twelve clinically healthy young subjects gave their informed consent to be studied. They were 6 men and 6 women ranging in age from 22 to 25 years. They were found to be healthy by an extensive clinical checkup.
Several investigations demonstrated that the renin-angiotensin-aldosterone system (RAAS) is constituted by biochemical variables that oscillate in human blood with a circadian periodicity {Gordon, Wolfe, Island and Liddle 1966; Vagnucci, McDonald, Drash and Wong 1974; Armbruster, Vetter, Beckerhoff, Nussberger and Vetter 1975; Katz, Romph and Smith 1975; Modlinger, Sharif-Zadeck, Ertel and Gutkin 1976; Cugini, Manconi, Serdoz, Mancini, Meucci and Scavo 1980; Kawasaki, Ueno, Uezono, Matsuoka, Omae, Halberg, Wendt, Taggett-Anderson and Haus 1980; Kawasaki, Uezono, Ueno, Omae, Matsuoka, Haus and Halberg 1983).
Each subject was investigated under controlled conditions of sodium (Na) and potassium (K) intake. The electrolyte balance was assessed by the urinary Na and K excretion rate (urinary Na: 175 + 16 mEq/day, urinary K: 35.5 ±2.5 mEq/day). Determinations of total renin concentration (TRC), active renin concentration (ARC), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were carried out in systemic venous blood drawn 8 times over a period of 25 hours starting at 0800. While the first blood sampling was done with subjects in sitting position and was utilized for a control of normalcy, the subsequent specimens were taken from 1200 to 0800 in subjects who were recumbent in horizontal position 1 hour prior to each blood collection. The last sampling at 0900 was done with
Horm.metab.Res.22(1990)636-639 © Georg Thieme Verlag Stuttgart • New York
Received: 3 Aug. 1989
Accepted: 3 May 1990
Downloaded by: National University of Singapore. Copyrighted material.
T. Kawasaki1, P. Cugini, K. Uezono , H. Sasaki1, K. Itoh3, M. Nishiura4 and K. Shinkawa4 Institute of Health Science, Kyushu University, Kasuga, Japan Endocrine Pathophysiology, University of Rome "La Sapienza", Rome, Italy Nakamura Gakuen College, Fukuoka, Japan 4Daiichi Radioisotope Laboratories Ltd., Tokyo, Japan
Horm. metab. Res. 22 (1990)
Circadian Rhythm of Total and Active Renin
Fig. 1 The model of cosinor analysis.
Degrees (360° = 24 h) no
_go°
-180°
-270°
-360° 1 1 1 1 1 1 1
Acrophase (0)
20 18
95 % confidence limits •
«, 16 E 14
Residual
•2
