Renal vascular response to interruption of the renin-angiotensin system in normal man

Renal vascular response to interruption of the renin-angiotensin system in normal man. We assessed the role of the renin-angiotensin system in the response of the renal circulation to restriction of sodium intake in 38 normal patients. Both saralasin (10 to 30 ng/kg/min), an angiotensin antagonist, and SQ 20881 (30 to 300µg/kg), a converting enzyme inhibitor, induced a dose-related increase in renal blood flow (xenon 133 washout) only when the renin-angiotensin system was activated by restriction of sodium intake to 10 mEq/day. Increasing doses of saralasin (100 to 1,000 ng/kg/min) reduced renal blood flow, presumably due to the angiotensin-like action of this partial agonist. The renal vascular response to SQ 20881 paralleled the endocrine response: An identical threshold dose (30µg/kg) increased renal blood flow and reduced plasma angiotensin II concentration, which fell despite a progressive rise of plasma renin activity. Plasma bradykinin concentration did not change in response to SQ 20881, which also blocks kininase II. Both agents also induced a small but consistent and statistically significant reduction in arterial blood pressure, which will be important in assessing the pathogenetic significance of a blood pressure reduction in patients with hypertension. This study indicates that angiotensin mediates the renal vascular response to restriction of salt intake in normal man and provides an approach to assessing the role played by angiotensin in the pathogenesis of functional renal disease. Reponse vasculaire du rein a l'interruption du systeme renine-angiotensine chez l'homme normal. Nous avons evalue le role du systeme renine-angiotensine dans la reponse de la circulation renale a la restriction de l'apport de sodium chez 38 sujets normaux. La saralasine (10 a 30 ng/kg/min), un antagoniste de l'angiotensine, de meme que le SQ 20881 (30 a 300 µg/kg), un inhibiteur de l'enzyme de conversion, determinent une augmentation du debit sanguin renal (lavage au 133 Xe) proportionnelle a la dose, mais seulement quand l'apport alimentaire est reduit jusqu'a 10 mEq/jour. L'augmentation des doses de saralasine (100 a 1,000 ng/kg/min) diminue le debit sanguin renal, probablement du fait de l'action de type angiotensine de cet agoniste partiel. La reponse vasculaire renale au SQ 20881 est parallele a la reponse endocrinienne: une dose seuil identique (30µg/kg) augmente le debit sanguin renal et diminue la concentration plasmatique d'angiotensine, qui decroit malgre une augmentation progressive de l'activite renine plasmatique. La concentration plasmatique de bradykinine ne change pas lors de l'administration de SQ 20881, qui bloque aussi la kininase II. Les deux agents etudies determinent une diminution faible, mais significative, de la pression arterielle. Ce fait sera important dans 1'evaluation de la signification pathogenique d'une diminution de la pression arterielle chez des malades atteints d'hypertension. Ce travail montre que l'angiotensine est un mediateur de la reponse vasculaire renale a la restriction de l'apport de sodium chez l'homme, et il fournit une approche de 1'evaluation du role de l'angiotensine dans la pathogenie des alterations fonctionnelles du rein.