Laboratory Investigation

Kidney International (1975) 7, 331–341; doi:10.1038/ki.1975.46

Reaction constants of renin in juxtaglomerular apparatus and plasma renin activity after renal ischemia and hemorrhage

Peter Weber1, Eckhard Held1, Eike Uhlich1 and Jochen O C Eigler1

1II. Medizinische Klinik der Universität, Munich, West Germany

Correspondence: Dr Peter C Weber, II. Medizinische Klinik der Universität, Ziemssenstrasse 1, 8, München 2, West Germany.

Received 5 July 1974; Revised 29 October 1974.

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Abstract

Reaction constants of renin in juxtaglomerular apparatus and plasma renin activity after renal ischemia and hemorrhage. During and after total renal ischemia and acute hemorrhage, renin activity in plasma (PRA) and microdissected juxtaglomerular apparatus (JGA) of rabbits were investigated. In controls, the apparent Michaelis-Menten constant (MMC) of semipurified standard renin of rabbits was 1025 plusminus 233 SD ng/ml. Plasma renin of normal rabbits showed similar values: 1062 plusminus 138 SD ng/ml. Intrarenal JGA renin, however, showed a great scatter of MMC (920 to 4760 ng/ml) and a significantly higher mean value of 2572plusminus 1156 SD ng/ml (P<0.001). After complete renal ischemia by clamping both renal arteries for a 90-min period, the following results were obtained : 1) Sixty min after the beginning of ischemia, PRA decreased from 20.9 plusminus 9.8 SD to 7.6 plusminus 5.2 SD ng/ml dot hr(P < 0.05) and increased to 103, 68 and 42 ng/ml dot hr 10, 30 and 90 min after removal of the clamps, respectively (P < 0.05). 2) No significant change of JGA renin concentration was found 0 to 72 hr after ischemia (68.5 plusminus 73.0 to 65.6 plusminus 49.0; P > 0.1). 3) JGA renin activity increased significantly as indicated by a decrease of MMC from 2620 plusminus 1091 SD to 1305 plusminus 429 SD ng/ml, 30 to 90 min after ischemia (P < 0.002). After lowering mean arterial blood pressure from 85 plusminus 10 SD to 40 plusminus 16 SD mm Hg by acute hemorrhage, the following findings were registered : 1) PRA rose significantly from 18.1 plusminus 10.5 SD to 81.2 plusminus 35.6 ng/ml dot hr (P < 0.001) and reached control values after retransfusion. 2) JGA renin concentration decreased from 89.4 plusminus 42.1 SD to 45.2 plusminus 36.4 SD ng/100 micro1 dot hr per single JGA (P < 0.01). 3) The MMC of JGA renin decreased from 2620 plusminus 1091 sd to 1444 plusminus 358 SD ng/ml (P < 0.002). This suggests a transformation of JGA renin to a higher affinity form by these maneuvers. Our results indicate that, in addition to increased renin release into the systemic circulation, JGA renin activity is increased after renal ischemia and acute hemorrhage; this activation is not mediated by an elevation of enzyme concentration but by a decrease of MMC.

Constantes de réaction de la rénine de l'appareil juxta-glomérulaire et activité rénine plasmatique après ischémie rénale et hémorragie. Pendant et après l'ischémie rénale totale et après une hémorragie aiguë les activités rénine du plasma (PRA) et des appareils juxta-glomérulaires microdisséqués (JGA) de lapin ont été étudiées. Chez les contrôles la constante apparente de Michaelis Menten (MMC) de rénine standard semi-purifiée de lapins est de 1025 plusminus 233 SD ng/ml. La rénine plasmatique de lapin donne des valeurs semblables: 1062 plusminus 138 SD ng/ml. La rénine intrarénale des JGA, cependant, a une grande dispersion de MMC (920 à 4760 ng/ml) et une valeur moyenne significativement supérieure de 2572 plusminus 1156 SD ng/ml (P < 0,001). Après ischémie rénale totale par clampage des deux artères rénales pendant 90 min les résultats suivants ont été obtenus : 1) Soixante minutes après le début de l'ischémie PRA diminue de 20,9 plusminus 9,8 SD à 7,6 plusminus 5,2 SD ng/ml dot hr (P < 0,05) et augmente à 103, 68 et 42 ng/ml dot hr 10, 30 et 90 min, respectivement, après l'ablation des clamps (P < 0,05). 2) Aucune modification significative de la concentration de rénine dans les JGA n'est trouvée à 0 et 72 heures d'ischémie (68,5 plusminus 73,0 et 65,6 plusminus 49,0; P < 0,1). 3) L'activité rénine des JGA augmente significativement comme l'indique une diminution de MMC de 2620 plusminus 1091 SD à 1305 plusminus 429 SD ng/ml 30 et 90 min après l'ischémie (P < 0,002). Après l'abaissement de la pression artérielle moyenne de 85 plusminus 10 SD à 40 plusminus 16 SD mm Hg par une hémorragie aiguë les résultats suivants ont été obtenus: 1) PRA augmente significativement de 18,1 plusminus 10,5 SD à 81,2 plusminus 35,6 ng/ml dot hr (P < 0,001) et revient aux valeurs basales après transfusion; 2) La concentration de rénine dans JGA diminue de 89,4 plusminus 42,1 SD à 45,2 plusminus 36,4 SD ng/100 microl dot hr par JGA (P < 0,01). 3) La MMC des JGA diminue de 2620 plusminus 1091 SD à 1444 plusminus 358 SD ng/ml (P < 0,002). Cela suggère une transformation par ces manoeuvres, de la rénine des JGA, en une forme de plus grande affinité. Nos résultats indiquent qu'en plus d'une augmentation de la libération de rénine dans la circulation systémique, l'activité rénine des JGA est augmentée après l'ischémie rénale et l'hémorragie aiguë; cette activation n'est pas le fait d'une augmentation de la concentration de l'enzyme mais d'une diminution de la MMC.

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