Renin release in response to Renin system blockade: activation of the Renin system in type 1 diabetes mellitus.
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.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. rachko@aol.com
Radomir D
RD
Stevanovic
Deborah A
DA
Price
M Cecilia
MC
Lansang
Naomi Dl
ND
Fisher
Lori Mb
LM
Laffel
Norman K
NK
Hollenberg
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds; D002216:Captopril / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000627:therapeutic use; D014882:Water-Electrolyte Balance / Q000187:drug effects; D010130:p-Aminohippuric Acid / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D002216:Captopril; D012083:Renin; C081643:candesartan; D010130:p-Aminohippuric Acid