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Effects of ACE inhibition and AT1-receptor blockade on haemodynamic responses to L-arginine in Type 1 diabetes

Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, radko.komers@ medicon.cz

Renata Simkova

Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Ludmila Kazdova

Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Jana Ruzickova

Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Terezie Pelikanova

Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Introduction 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.

Key Words: angiotensin-converting enzyme inhibitors • angiotensin receptor blockers • L-arginine • blood pressure • diabetes • renal haemodynamics

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