Laboratory Investigation

Kidney International (1980) 18, 746–753; doi:10.1038/ki.1980.193

Indirect evidence against a role of the kinin system in the renal hemodynamic effect of captopril in the rat

Albert Mimran1, Daniel Casellas1 and Madeleine Dupont1

1Centre Hospitalier Universitaire, Montpellier, France

Correspondence: Dr Albert Mimran, Departement of Medicine D, Cliniques Saint-Charles, 34059 Montpellier, Cedex, France

Received 6 August 1979; Revised 31 March 1980.

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Abstract

Indirect evidence against a role of the kinin system in the renal hemodynamic effect of captopril in the rat. The effects of acute saralasin (SAR) and captopril (SQ) administration on arterial pressure (AP), plasma renin activity (PRA), urinary excretion of water and electrolytes, glomerular filtration rate (GFR), renal blood flow (RBF), and glomerular blood flow (GBF) distribution (microsphere technique) were assessed in rats with activation of the renal renin and kallikrein systems (that is, chronic sodium depletion). In both groups AP decreased, and PRA and RBF increased markedly. Blood flow to outermost (C1) glomeruli was (in nl/min/g of kidney wt) 270 plusminus 35 in SAR and 219 plusminus 20 in the SQ group (NS when compared to 208 plusminus 9 in control chronically sodium-depleted rats). Blood flow to innermost glomeruli (C4) strikingly increased from 95 plusminus 10 (control) to 216 plusminus 21 (SAR) and 180 plusminus 13 (SQ group). Hence, preferential vasodilatation of innermost glomeruli occurred (C1/C4 ratio of 2.18 plusminus 0.27 in control, 1.26 plusminus 0.11 in SAR, and 1.25 plusminus 0.07 in SQ rats). Chronic (6 days) administration of SQ was associated with a rapid and marked increase in water and sodium excretion. At the end of the study, RBF was higher than control, and GBF distribution was similar to that observed in acutely treated rats (C1/C4 ratio of 1.16 plusminus 0.10). These results suggest that angiotensin plays a significant role in the systemic and renal hemodynamic changes associated with chronic sodium depletion. The similarity of the changes induced by SAR and SQ provides an indirect evidence against an effective role of the renal kallikrein system in the effect of captopril.

Argument indirect contre le rôle du système kallicréine-kinine dans l'effet hémodynamique rénal du captopril. Les effets de l'administration aiguë de saralasine (SAR) et de captopril (SQ) sur la pression artérielle (AP), l'activité rénine plasmatique (PRA), l'excrétion urinaire de l'eau et des électrolytes, le taux de filtration glomérulaire (GFR), le flux sanguin rénal (RBF), et la distribution (technique des microsphères) des flux sanguins glomérulaires (GBF) ont été estimés chez des rats dont les systèmes rénine-angiotensine et kallicréine rénaux ont été activés par la déplétion sodée chronique. Dans les deux groupes (SAR et SQ), la AP a diminué et l'PRA et le RBF ont augmenté de façon similaire. Le flux sanguin des glomérules les plus superficiels (C1) (en nl/min/g rein) était de 270 plusminus 35 chez les animaux du groupe SAR et 219 plusminus 20 dans le groupe SQ (NS par rapport à la valeur 208 plusminus 9 du groupe de rats contrôles dépiétés chroniquement en sodium). Le flux des glomérules les plus profonds (C4) augmente de façon nette de 95 plusminus 10 (contrôle) à 216 plusminus 21 (SAR) et à 180 plusminus 13 (SQ). Ces résultats suggèrent une vasodilatation préférentielle des glomérules profonds (rapport C1/C4 de 2.18 plusminus 0.27 pour le groupe contrôle, 1.26 plusminus 0.11 pour le groupe SAR, et 1.25 plusminus 0.07 pour les rats traités par SQ). L'administration chronique (6 jours) de SQ a été associée à une augmentation rapide de l'excrétion d'eau et de sodium. A la fin de l'étude le RBF était supérieur à la valeur contrôle et la distribution des GBF était semblable à celle observée chez les animaux traités en aigu (rapport C1/C4 = 1.16 plusminus 0.10). Ces résultats suggèrent que l'angiotensine joue un rôle significatif dans les variations hémodynamiques systémiques et rénales associées à la déeplétion sodée chronique. La similarité des modifications induites par SAR et SQ constitue un argument indirect contre la médiation des effets du captopril par le système kallicréine-kinine rénal.

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