Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis

Abhiram Prasad, Theresa Tupas-Habib, William H. Schenke, Rita Mincemoyer, Julio A. Panza, Myron A. Waclawin, Samer Ellahham, Arshed A. Quyyumi

Research output: Contribution to journalArticle

177 Scopus citations

Abstract

Background - The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The present study was performed to determine whether angiotensin-1 (AT1) receptor inhibition improves endothelial dysfunction. Methods and Results - In the femoral circulation of 19 patients with atherosclerosis and of 9 control subjects, we studied microvascular responses to reactive hyperemia, angiotensin II, acetylcholine, and sodium nitroprusside before and after the administration of intra-arterial losartan (10 mg). Femoral artery flow velocity was measured with a Doppler flow wire, and the femoral vascular resistance index (FVRI) was calculated as mean arterial pressure divided by flow velocity. Losartan induced a minor (5.9±2%, P=0.02) reduction in FVRI and inhibited angiotensin II-mediated vasoconstriction in both patient groups (P<0.01). After the administration of losartan, acetylcholine-mediated vasodilation was augmented in patients (44±5% to 58±4% reduction in FVRI with infusion at a rate of 150 μg/min, P<0.001) but not control subjects. Vasodilation during reactive hyperemia was also greater after AT1 receptor inhibition (P=0.03) in patients, but the response to sodium nitroprusside remained unchanged. In a separate group of 31 patients with atherosclerosis, we investigated the effect of 8 weeks of oral losartan therapy on brachial artery flow-mediated vasodilation with the use of high-resolution ultrasound. Oral losartan therapy improved flow-mediated brachial artery dilation (1.4±0.9% to 3.2±0.8%, P=0.03) but had no effect on the nitroglycerin response. Serum nitrogen oxide levels increased from 21.6±1.7 to 26.7±2.4 μmol/L (P=0.008). Conclusions - The results of the present study indicate that inhibition of the AT1 receptor in patients with atherosclerosis reverses endothelial dysfunction by improving NO availability and therefore may have long-term therapeutic benefits.

Original languageEnglish (US)
Pages (from-to)2349-2354
Number of pages6
JournalCirculation
Volume101
Issue number20
DOIs
StatePublished - May 23 2000

Keywords

  • Angiotensin
  • Atherosclerosis
  • Endothelium
  • Losartan
  • Nitric oxide
  • Receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis'. Together they form a unique fingerprint.

  • Cite this

    Prasad, A., Tupas-Habib, T., Schenke, W. H., Mincemoyer, R., Panza, J. A., Waclawin, M. A., Ellahham, S., & Quyyumi, A. A. (2000). Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis. Circulation, 101(20), 2349-2354. https://doi.org/10.1161/01.CIR.101.20.2349