Enalapril Is Superior to Lisinopril in Improving Endothelial Function without a Difference in Blood–Pressure–Lowering Effects in Newly Diagnosed Hypertensives

Nagy, Attila and Májer, Réka and Boczán, Judit and Sipka, Sándor and Szabó, Attila and Enyedi, Enikő Edit and Tatai, Ottó and Fagyas, Miklós and Papp, Zoltán and Csiba, László and Tóth, Attila (2023) Enalapril Is Superior to Lisinopril in Improving Endothelial Function without a Difference in Blood–Pressure–Lowering Effects in Newly Diagnosed Hypertensives. BIOMEDICINES, 11 (12). No. 3323. ISSN 2227-9059

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Abstract

Angiotensin–converting enzyme (ACE) inhibitors are the primarily chosen drugs to treat various cardiovascular diseases, such as hypertension. Although the most recent guidelines do not differentiate among the various ACE inhibitory drugs, there are substantial pharmacological differences. Goal: Here, we tested if lipophilicity affects the efficacy of ACE inhibitory drugs when used as the first therapy in newly identified hypertensives in a prospective study. Methods: We tested the differences in the cardiovascular efficacy of the hydrophilic lisinopril (8.3 + 3.0 mg/day) and the lipophilic enalapril (5.5 + 2.3 mg/day) (n = 59 patients). The cardiovascular parameters were determined using sonography (flow-mediated dilation (FMD) in the brachial artery, intima-media thickness of the carotid artery), 24 h ambulatory blood pressure monitoring (peripheral arterial blood pressure), and arteriography (aortic blood pressure, augmentation index, and pulse wave velocity) before and after the initiation of ACE inhibitor therapy. Results: Both enalapril and lisinopril decreased blood pressure. However, lisinopril failed to improve arterial endothelial function (lack of effects on FMD) when compared to enalapril. Enalapril-mediated improved arterial endothelial function (FMD) positively correlated with its blood–pressure–lowering effect. In contrast, there was no correlation between the decrease in systolic blood pressure and FMD in the case of lisinopril treatment. Conclusion: The blood–pressure–lowering effects of ACE inhibitor drugs are independent of their lipophilicity. In contrast, the effects of ACE inhibition on arterial endothelial function are associated with lipophilicity: the hydrophilic lisinopril was unable to improve, while the lipophilic enalapril significantly improved endothelial function. Moreover, the effects on blood pressure and endothelial function did not correlate in lisinopril-treated patients, suggesting divergent mechanisms in the regulation of blood pressure and endothelial function upon ACE inhibitory treatment.

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