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

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 (K f ) that occurs in single glomeruli in response to infusion of these substances. Less clear is the mechanism whereby similar declines in K f are induced with infusions of dibutyryl cyclic AMP (DBcAMP), parathyroid hormone (PTH), and prostaglandins, because PTH and PGE 2 , at least, are incapable of eliciting mesangial cell contraction in vitro. To further explore the factors that regulate K f in vivo, we performed micropuncture experiments in 47 euvolemic Munich-Wistar rats. Infusions of DBcAMP, PTH, prostaglandins I 2 and E 2 led to lower mean values for plasma flow rate (Q A ) and K f in superficial glomeruli than were found in animals given vehicle alone (control group), whereas average values for glomerular transcapillary hydraulic pressure difference (ΔP) and total renal arteriolar resistance (R TA ) tended to be higher. These increases in ΔP and R TA , and decreases in Q A and K f , with DBcAMP, PTH, PGI 2 , and PGE 2 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 ΔP, Q A R TA , and K f were largely abolished. Therefore, the actions of DBcAMP, PTH, PGI 2 , and PGE 2 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 K f , 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 K f . Mecanismes de l'action de differentes hormones et substances vasoactives sur l'ultrafiltration glomerulaire chez le rat. L'angiotensine II (AII) et l'arginine vasopressine peuvent declencher in vitro une contraction des cellules mesangiales glomerulaires. Un mecanisme semblable qui agirait in vivo et reduirait la surface du capillaire glomerulaire pourrait expliquer la diminution du coefficient d'ultrafiltration (K f ) qui survient dans les glomerules isoles en reponse a la perfusion de ces substances. Le mecanisme par lequel des diminutions semblables de K f sont determinees par des perfusions de dibutyryl cAMP (DBcAMP), d'hormone parathyroidienne (PTH) et de prostaglandines est moins clair puisqu'au moins PTH et PGE 2 sont incapables de declencher la contraction des cellules mesangiales in vitro. Afin de mieux explorer les facteurs qui regulent K f in vivo, des experiences de micro-ponctions ont ete realisees chez 47 rats Munich-Wistar euvolemiques. Les perfusions de DBcAMP, PTH, prostaglandines I 2 et E 2 ont entraine une diminution du debit plasmatique (Q A ) et du K f dans les glomerules superficiels par rapport aux animaux ne recevant que le vehicule (groupe controle) alors que les valeurs moyennes de la difference de pression hydraulique transcapillaire, , et la resistance arteriolaire totale, R TA , tendaient a etre plus elevees. Ces augmentations de et R TA et les diminutions de Q A et K f avec DBcAMP, PTH, PGI 2 et PGE 2 sont typiques des modifications induites par AII En effet, quand la saralasine, un antagoniste competitif de AII, a ete perfusee en meme temps que ces differentes substances vaso-actives, les effets sur , Q A , R TA , et K f ont ete en grande partie abolis. Ainsi les actions de DBcAMP, PTH, PGI 2 , et PGE 2 sur la microcirculation glomerulaire paraissent dependre d'une action intermediaire de AII Au contraire, bien que la perfusion d'ADH determine aussi une diminution significative de K f , l'administration de saralasine n'abolit pas cette modification, ce qui suggere que l'action de l'ADH sur la microcirculation glomerulaire ne depend pas d'une voie impliquant l' AII. Sur la base de ces etudes il semble raisonnable de proposer que AII et ADH soient a la fois des regulateurs importants de la contraction des cellules mesangiales et, de ce fait, de la surface de filtration glomerulaire et de K f .