Renal response to angiotensin after short-term angiotensin converting enzyme inhibition.
In 13 normotensive subjects on a normal sodium diet, we studied hormonal, blood pressure, and renal vascular changes and dextran sieving profiles induced by infusion of exogenous angiotensin II (Ang II) (5 ng.kg-1.min-1). during baseline conditions and after 5 days of administration of the angiotensin converting enzyme inhibitor cilazapril. Cilazapril induced a renal vasodilative effect without affecting supine blood pressure and glomerular filtration rate. Fractional dextran clearances were significantly decreased for dextran of effective radius ranging from 3.0 to 4.0 nm. This shift was primarily related to an increase in glomerular capillary plasma flow, because no change was observed in the transcapillary glomerular pressure gradient, the ultrafiltration coefficient, or the membrane parameters. Ang II elicited a slight pressor response accompanied by hormonal, antinatriuretic, and renal hemodynamic changes that were similar during and before short-term angiotensin converting enzyme inhibition. Dextran sieving curves were unchanged by a low dose of Ang II. However, the transcapillary glomerular pressure gradient and the ultrafiltration coefficient were computed to increase by 19.4% and to decrease by 44.2%, respectively, whereas membrane parameters were unaffected. When superimposed onto short-term angiotensin converting enzyme inhibition, glomerular response to this unique dose of Ang II was similar to that induced by Ang II alone. These findings indirectly suggest that most, if not all, of the renal effects of cilazapril are mediated through suppression of Ang II formation.
Hannedouche
T
T
Department of Nephrology, Hôpital Necker, Paris, France.
Schmitt
F
F
Ikeni
A
A
Marques
L P
LP
Natov
S
S
Déchaux
M
M
Lacour
B
B
Grünfeld
J P
JP
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D017315:Cilazapril / Q000494:pharmacology; D003911:Dextrans / Q000493:pharmacokinetics; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008297:Male; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D003911:Dextrans; D000804:Angiotensin II; D017315:Cilazapril; D012964:Sodium