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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: Jan Wysocki; Minghao Ye; Ahmed M Khattab; Agnes Fogo; Aline Martin; Nicolae Valentin David; Yashpal Kanwar; Mark Osborn; Daniel Batlle Journal: Kidney Int Date: 2016-12-04 Impact factor: 10.612
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Authors: Jenifer M Brown; Jonathan S Williams; James M Luther; Rajesh Garg; Amanda E Garza; Luminita H Pojoga; Daniel T Ruan; Gordon H Williams; Gail K Adler; Anand Vaidya Journal: Hypertension Date: 2013-11-04 Impact factor: 10.190
Authors: Jan Wysocki; Laura Garcia-Halpin; Minghao Ye; Christoph Maier; Kurt Sowers; Kevin D Burns; Daniel Batlle Journal: Am J Physiol Renal Physiol Date: 2013-06-12
Authors: Patrick N Cunningham; Zhiying Wang; Megan L Grove; Rhonda M Cooper-DeHoff; Amber L Beitelshees; Yan Gong; John G Gums; Julie A Johnson; Stephen T Turner; Eric Boerwinkle; Arlene B Chapman Journal: PLoS One Date: 2019-09-18 Impact factor: 3.240
Authors: Bibi S van Thiel; Janette van der Linden; Yanto Ridwan; Ingrid M Garrelds; Marcel Vermeij; Marian C Clahsen-van Groningen; Fatimunnisa Qadri; Natalia Alenina; Michael Bader; Anton J M Roks; A H Jan Danser; Jeroen Essers; Ingrid van der Pluijm Journal: Int J Mol Sci Date: 2021-11-18 Impact factor: 5.923