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Renin Release in Response to Renin System Blockade: Activation of the Renin System in Type 1 Diabetes Mellitus
Radomir D Stevanovic
Departments of Medicine and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA, rachko{at}aol.com
Deborah A Price
Departments of Medicine and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
M Cecilia Lansang
Departments of Medicine and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Naomi DL Fisher
Departments of Medicine and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Lori MB Laffel
Joslin Diabetes Center, Harvard School of Medicine, Boston, Massachusetts, USA
Norman K Hollenberg
Departments of Medicine and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Activation of the renin-angiotensin system (RAS) in diabetes is thought to contribute to nephropathy. This is suggested by findings of an enhanced renovascular (RPF) response to RAS blockade with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs). An alternative approach to assess RAS activation is the evaluation of renin release following RAS blockade.
Forty-four consecutively enrolled Type 1 diabetic patients (28.2 ± 1.5 years) and 37 normal subjects (37 ± 2.6 years) in high salt balance were given 25 mg of captopril and 16 mg of candesartan p.o. on consecutive days. All subjects were Caucasian. All, except one diabetic patient, had normal renal function. Plasma renin activity (PRA) and renal plasma flow (RPF) were measured for four hours after both drugs, and at eight, and 24 hours after candesartan.
As anticipated, both drugs increased PRA. Peak responses (90' after captopril) were 5.6 ± 1 ng/mL Ang I/hour in diabetic patients, and 1.7 ± 0.9 ng/mL Ang I/hour in normal subjects (p<0.001). Responses to both drugs were correlated in diabetic patients for PRA (r=0.623; p=0.001) and for RPF (r=0.9; p<0.001). When the PRA response to captopril was below the median, the RPF response was limited (22.1 ± 17.6 ml/minute/1.73 m2). When it was above the median, the RPF response was also larger (62.2 ± 13.9 ml/minute/1.73 m2; p=0.006).
Renin response to ACE-I and ARB confirms activation of the RAS in diabetic patients.
Key Words: Diabetes • Renin • Renal plasma flow
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Journal of Renin-Angiotensin-Aldosterone System, Vol. 6, No. 2,
78-83 (2005)
DOI: 10.3317/jraas.2005.013
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