Renal response to captopril reflects state of local renin system in healthy humans.
BACKGROUND
Heightened activity of the renin-angiotensin system has been linked to the development of both essential hypertension and diabetic nephropathy. Blunting of the renal vasoconstrictor response to Ang II, specifically when it is corrected by angiotensin converting enzyme (ACE) inhibition, is a feature which we have employed as a marker for activation of the intrarenal RAS. In this study we tested the hypothesis that variation in the renal vasodilator response to ACE inhibition in healthy humans reflected the variation in angiotensin-mediated renal vasoconstriction provoked by a low-salt diet.


METHODS
We studied 20 healthy people (ages 19 to 57; 15 males) who were in balance on a low sodium diet. Ang II was infused for 45 minutes (3 ng/kg/min), followed by 25 mg captopril and a repeat Ang II infusion; PAH clearance was measured at the end of each interval.


RESULTS
All subjects responded to captopril with a rise in renal plasma flow (range 43 to 242, mean 118 + 12 ml/min/1.73 m2). Individual vasodilator response to captopril was a strong inverse predictor of the precaptopril vasoconstrictor response to Ang II (P = 0.006, r = -0.59). There was a stronger, positive correlation of the vasodilator response to captopril and enhancement of Ang II responsiveness after captopril (r = 0.57). Plasma renin activity was significantly correlated with captopril response among the large responders (P = 0.003; r = 0.83), but not at all among those with little response.


CONCLUSIONS
These results suggest substantial variation in angiotensin-mediated control of the renal circulation in healthy individuals on a low sodium intake. Variation in the vasodilator response to captopril, correlated with responses to Ang II, provides a measure of that control.
Fisher
N D
ND
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ndfisher@bics.bwh.harvard.edu
Price
D A
DA
Litchfield
W R
WR
Williams
G H
GH
Hollenberg
N K
NK
D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000808:Angiotensinogen / Q000378:metabolism; D002216:Captopril / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D000806:Angiotensin-Converting Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D000808:Angiotensinogen; D000804:Angiotensin II; D002216:Captopril; D012083:Renin; D010130:p-Aminohippuric Acid