title: Impacts of lisinopril and lisinopril plus simvastatin on erythrocyte and plasma arginase, nitrite, and nitrate in hypertensive patients.
abstract: Angiotensin-converting enzyme inhibitors are effective at reducing blood pressure, whereas statins decrease plasma cholesterol, impeding atherosclerosis. The authors hypothesize that these medications may improve blood pressure by modifying the arginase-nitric oxide synthase system of erythrocytes. In this study, the effects of lisinopril alone versus lisinopril + simvastatin on erythrocyte and plasma arginase enzyme and nitric oxide metabolites are compared. Patients with atherosclerosis and hypertension are randomly assigned to receive lisinopril 10 to 20 mg/d or lisinopril 10 to 20 mg/d plus simvastatin 20 mg/d for 24 weeks. Higher arginase activity is observed in erythrocytes from 100% of patients and mainly recovered after 12 and 24 weeks of treatment with lisinopril or lisinopril + simvastatin. Plasma arginase activity is 3 orders of magnitude lower than erythrocyte arginase activity in all participants, suggesting a lack of its clinical significance. Both treatments cause the increase in plasma                   $$\hbox{ N }{\hbox{ O }}_{2}^{-}$$               ,                   $$\hbox{ N }{\hbox{ O }}_{3}^{-}$$               , and                   $$\hbox{ N }{\hbox{ O }}_{2}^{-}$$                +                   $$\hbox{ N }{\hbox{ O }}_{3}^{-}$$                in 100% of patients. Erythrocyte                   $$\hbox{ N }{\hbox{ O }}_{2}^{-}$$                +                   $$\hbox{ N }{\hbox{ O }}_{3}^{-}$$                concentration is greatly decreased in hypertensive patients but recovers after monotherapy and combined therapy. The results show for the first time that lisinopril monotherapy and combined lisinopril + simvastatin therapy exhibit pronounced and equipotential normalizing effects on erythrocyte arginase and nitric oxide synthase activities.
authors.affiliation: Institute of Theoretical and Experimental Biophysics, RAS, Pushchino, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Kosenko
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Tikhonova
authors.forename: Alexander
authors.initials: A
authors.lastname: Suslikov
authors.forename: Yury
authors.initials: Y
authors.lastname: Kaminsky
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001119:Arginase / Q000097:blood; D050197:Atherosclerosis / Q000097:blood* / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D017706:Lisinopril / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009566:Nitrates; D009573:Nitrites; D019821:Simvastatin; D017706:Lisinopril; D001119:Arginase