Laboratory Investigation

Kidney International (1981) 20, 442–451; doi:10.1038/ki.1981.160

Mechanisms of action of various hormones and vasoactive substances on glomerular ultrafiltration in the rat

Nestor Schor, Iekuni Ichikawa and Barry M Brenner

Laboratory of Kidney and Electrolyte Physiology and Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Correspondence: Dr B M Brenner, Renal Division, Brigham and Women's Hospitals, 75 Francis Street, Boston, Massachusetts, 02115, USA

Received 14 October 1980; Revised 19 December 1980.

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Abstract

Mechanisms of action of various hormones and vasoactive substances on glomerular ultrafiltration in the rat. Angiotensin II (AII) and arginine vasopressin are capable of triggering glomerular mesangial cell contraction in vitro. A similar mechanism acting in vivo to reduce glomerular capillary surface area could account for the decline in the ultrafiltration coefficient (Kf) that occurs in single glomeruli in response to infusion of these substances. Less clear is the mechanism whereby similar declines in Kf are induced with infusions of dibutyryl cyclic AMP (DBcAMP), parathyroid hormone (PTH), and prostaglandins, because PTH and PGE2, at least, are incapable of eliciting mesangial cell contraction in vitro. To further explore the factors that regulate Kf in vivo, we performed micropuncture experiments in 47 euvolemic Munich-Wistar rats. Infusions of DBcAMP, PTH, prostaglandins I2 and E2 led to lower mean values for plasma flow rate (QA) and Kf in superficial glomeruli than were found in animals given vehicle alone (control group), whereas average values for glomerular transcapillary hydraulic pressure difference (DeltaP) and total renal arteriolar resistance (RTA) tended to be higher. These increases in DeltaP and RTA, and decreases in QA and Kf, with DBcAMP, PTH, PGI2, and PGE2 are typical of changes induced by AII. Indeed, when saralasin, a competitive AII antagonist, was infused together with these various vasoactive substances, the effects on DeltaP, QA RTA, and Kf were largely abolished. Therefore, the actions of DBcAMP, PTH, PGI2, and PGE2 on the glomerular microcirculation appear to depend on an intermediate action of AII. By contrast, although pitressin (ADH) infusion also led to a significant decline in Kf, saralasin administration did not reverse this change, suggesting that the action of ADH on the glomerular microcirculation is independent of a pathway involving AII. Based on these studies, it seems reasonable to propose that AII and ADH are both potentially important regulators of mesangial cell contraction, and thereby, glomerular capillary filtering surface area and Kf.

Mécanismes de l'action de différentes hormones et substances vasoactives sur l'ultrafiltration glomérulaire chez le rat. L'angiotensine II (AII) et l'arginine vasopressine peuvent déclencher in vitro une contraction des cellules mésangiales glomérulaires. Un mécanisme semblable qui agirait in vivo et réduirait la surface du capillaire glomérulaire pourrait expliquer la diminution du coefficient d'ultrafiltration (Kf) qui survient dans les glomérules isolés en réponse à la perfusion de ces substances. Le mécanisme par lequel des diminutions semblables de Kf sont déterminées par des perfusions de dibutyryl cAMP (DBcAMP), d'hormone parathyroïdienne (PTH) et de prostaglandines est moins clair puisqu'au moins PTH et PGE2 sont incapables de déclencher la contraction des cellules mésangiales in vitro. Afin de mieux explorer les facteurs qui régulent Kf in vivo, des expériences de micro-ponctions ont été réalisées chez 47 rats Munich-Wistar euvolémiques. Les perfusions de DBcAMP, PTH, prostaglandines I2 et E2 ont entraîné une diminution du débit plasmatique (QA) et du Kf dans les glomérules superficiels par rapport aux animaux ne recevant que le véhicule (groupe contrôle) alors que les valeurs moyennes de la différence de pression hydraulique transcapillaire, DeltaP, et la résistance artériolaire totale, RTA, tendaient à être plus élevées. Ces augmentations de DeltaP et RTA et les diminutions de QA et Kf avec DBcAMP, PTH, PGI2 et PGE2 sont typiques des modifications induites par AII En effet, quand la saralasine, un antagoniste compétitif de AII, a été perfusée en même temps que ces différentes substances vaso-actives, les effets sur DeltaP, QA, RTA, et Kf ont été en grande partie abolis. Ainsi les actions de DBcAMP, PTH, PGI2, et PGE2 sur la microcirculation glomérulaire paraissent dépendre d'une action intermédiaire de AII Au contraire, bien que la perfusion d'ADH détermine aussi une diminution significative de Kf, l'administration de saralasine n'abolit pas cette modification, ce qui suggère que l'action de l'ADH sur la microcirculation glomérulaire ne dépend pas d'une voie impliquant l' AII. Sur la base de ces études il semble raisonnable de proposer que AII et ADH soient à la fois des régulateurs importants de la contraction des cellules mésangiales et, de ce fait, de la surface de filtration glomérulaire et de Kf.

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