title: Replacement of angiotensin-converting enzyme inhibitors by angiotensin-II-receptor antagonists in hypertensive patients with type II diabetes mellitus: metabolic and hemodynamic consequences.
abstract: The main pharmacodynamic difference between angiotensin-converting enzyme-inhibitors (ACE-i) and angiotensin-II-receptor antagonists (AII-r) is that ACE-i increase levels of bradykinin, which, in addition to vasodilation, may cause a decrease in insulin resistance. Hypertensive patients with diabetes type II suffering from side effects from ACE-i are frequently changed over to AII-r. The objectives of this study were (1) to study whether this procedure reduces metabolic control, (2) to study effects on blood pressure and forearm blood flow (FLOW), and (3) to study possible associations between the variables hemoglobin A (1c) (HbA(1c)) and FLOW. A self-controlled sequential comparison is required to address such questions. Sixteen patients were treated with 10 mg enalapril or equipotent doses of other ACE-i for 6 months and subsequently with the AII-r losartan at 50 mg daily for 6 more months. Patients were examined at the outpatient clinic every 4 to 8 weeks during the trial. FLOW was measured by iridium strain gauge venous occlusion plethysmography. Mean arterial pressure (MAP) increased by 4 +/- 5 mm Hg (P <.05) after 6 months of losartan treatment as compared with the point of withdrawal of ACE-i. FLOW decreased by 5.4 +/- 5.0 mL/100 mL tissue/min (P <.001), and HbA (1c) increased by 0.6 +/- 0.8 mmol/L (P <.05). Other metabolic variables, including cholesterol, high-density lipoprotein cholesterol, and triglycerides, were not significantly influenced by the change in therapy. Multiple regression analysis revealed that after adjustment for difference in HbA (1c), the correlation between FLOW and MAP was unchanged, and after adjustment for difference in FLOW, the correlation between HbA (1c) and MAP was no longer significant. Replacement of ACE-i by AII-r in hypertensive patients with type II diabetes mellitus induced a significant increase in HbA (1c) and MAP and a decrease in FLOW. The associations of HbA (1c) and FLOW with MAP were at least partly independent of each other, suggesting that mechanisms other than the bradykinin system (eg, the angiotensin (2) -receptor system) are involved. Our study design did not control for placebo and time effects, and so the data are of a preliminary nature.
authors.affiliation: Department of Medicine, Merwede Hospital, Dordrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van der Meulen
authors.forename: T J
authors.initials: TJ
authors.lastname: Cleophas
authors.forename: A H
authors.initials: AH
authors.lastname: Zwinderman
mesh_terms: D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010991:Plethysmography; D012044:Regression Analysis; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D006442:Glycated Hemoglobin; D019808:Losartan