Low-density lipoprotein-cholesterol determines vascular responsiveness to angiotensin II in normocholesterolaemic humans

Stefan John, Christian Delles, Arnfried U. Klingbeil, Johannes Jacobi, Markus P. Schlaich, Roland E. Schmieder

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Abstract

Objective. Both LDL-cholesterol and angiotensin II have been shown to increase the risk for and severity of cardiovascular disease. In hypercholesterolaemia, experimental studies have demonstrated an increased angiotensin type 1 (AT1) receptor expression on vascular smooth muscle cells and an increased vascular responsiveness to vasopressors has been documented in humans, We investigated in a normocholesterolaemic young population whether vascular responsiveness to angiotensin II(Ang II) infusion depends on LDL-cholesterol serum levels in the systemic and renal circulation. Design and methods. Changes in systolic and diastolic blood pressure (ΔBP) to Ang II infusion (0.5 and 3.0 ng/kg per min) were investigated in 103 normocholesterolaemic (LDL-cholesterol < 160 mg/dl) young white men (26 ± 3 years; 24 h BP: 128 ± 10/75 ± 7 mmHg) without cardiovascular disease. According to their LDL-cholesterol levels, participants were classified into tertiles (lower tertile < 85 mg/dl, middle tertile 85-111 mg/dl, upper tertile > 111 mg/dl). Results. Blood pressure (BP) responses to Ang II infusion 3.0 ng/kg per min were enhanced in the group with the highest LDL-cholesterol levels (Δ systolic BP: + 12.8 ± 6.7, + 13.2 ± 8.6, + 17.9 ± 9.6, P < 0.02; Δ diastolic BP: + 11.1 ± 5.8, + 11.5 ± 6.5, + 16.5 ± 8.3, P < 0.01, for the lower, middle and upper tertiles, respectively). This holds true when baseline BP was taken into account as a confounding covariable (P < 0.015). BP responses to Ang II infusion were related to LDL-cholesterol serum levels (Δ systolic BP: r = 0.26, P = 0.01; Δ diastolic BP: r = 0.32, P = 0.001). In multiple stepwise regression analysis, LDL-cholesterol emerged as the strongest determinant of vascular responsiveness to Ang II (Δ systolic BP: P < 0.01; Δ diastolic BP: P < 0.001). Conclusion. In young male subjects, responsiveness to Ang II is determined by the LDL-cholesterol serum level even in the normal range of LDL-cholesterol, thereby potentially contributing to the cardiovascular risk of LDL-cholesterol even within the so-called normal range.

Original languageEnglish
Pages (from-to)1933-1939
Number of pages7
JournalJournal of Hypertension
Volume17
Issue number12 SUPPL.
Publication statusPublished - 1 Dec 1999
Externally publishedYes

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    John, S., Delles, C., Klingbeil, A. U., Jacobi, J., Schlaich, M. P., & Schmieder, R. E. (1999). Low-density lipoprotein-cholesterol determines vascular responsiveness to angiotensin II in normocholesterolaemic humans. Journal of Hypertension, 17(12 SUPPL.), 1933-1939.