Effects of ACE inhibition and AT1-receptor blockade on haemodynamic responses to L-arginine in Type 1 diabetes.
BACKGROUND
Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve endothelial function in Type 1 diabetes. However, the potential of ACE inhibitors (ACE-I) to enhance the haemodynamic effects of L-arginine (L-arg), the precursor of nitric oxide (NO), has not been evaluated. Furthermore, angiotensin receptor blockers (ARBs), another group of inhibitors of the renin-angiotensin system (RAS), have not been studied in this context.


METHODS
Using a randomised, crossover design, the acute effects of L-arg (200 mg/kg) on blood pressure (BP) and renal haemodynamics were determined in uncomplicated Type 1 diabetic patients before and after three weeks of treatment with the ACE-I ramipril (5 mg/day) or the ARB losartan (50 mg/day).


RESULTS
L-arg alone did not influence BP or renal haemodynamics. BP responses to L-arg were not modulated by ACE-I or ARB. In contrast to the systemic responses, L-arg induced significant renal vasodilation after treatment with ramipril (p<0.05). Unlike ramipril, losartan did not modulate renal haemodynamic responses to L-arg. L-arg administration was paralleled by increments in plasma L-citrulline levels, determined as a measure of L-arg-induced systemic NO production. These responses were not influenced by RAS inhibitors. No changes in other indicators of the systemic and renal NO production, such as plasma and urinary nitrates/nitrites, were detected in response to L-arg alone or after treatment with RAS inhibitors.


CONCLUSIONS
ACE-Is have greater potential than ARBs to enhance L-arg effects in the kidney in uncomplicated Type 1 diabetes. Neither RAS inhibitor influenced the systemic effects of L-arg. The lack of changes in renal NO indicators parallelling the haemodynamic responses, suggests that the effects of ACE-I on L-arg-induced renal haemodynamic changes could be also attributable to NO-independent mechanisms.
Komers
Radko
R
Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. radko.komers@medicon.cz
Simkova
Renata
R
Kazdova
Ludmila
L
Ruzickova
Jana
J
Pelikanova
Terezie
T
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001120:Arginine / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002956:Citrulline / Q000097:blood; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology*; D004357:Drug Synergism; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000097:blood; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D017257:Ramipril / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D006728:Hormones; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D019808:Losartan; D017257:Ramipril