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High Angiotensin II Responsiveness is Associated with Decreased Endothelium-Dependent Relaxation in Human Arteries

Department of Cardiology, University Medical Center Groningen, The Netherlands, a.a.voors{at}thorax.umcg.nl

Peter Paul van Geel

Department of Cardiology, University Medical Center Groningen, The Netherlands

Hendrik Buikema

Department of Clinical Pharmacology, University Medical Center Groningen, The Netherlands

Margreeth Oosterga

Department of Cardiology, University Medical Center Groningen, The Netherlands

Dirk J van Veldhuisen

Department of Cardiology, University Medical Center Groningen, The Netherlands

Wiek H van Gilst

Department of Clinical Pharmacology, University Medical Center Groningen, The Netherlands

Introduction. Animal studies demonstrated an interaction between angiotensin II (Ang II) responsiveness and endothelium-dependent relaxation (EDR). However, this relation has not been well described in humans. Therefore, we investigated the relation between Ang II responsiveness and EDR in isolated human arteries.

Materials and Methods. Segments of the internal mammary artery (IMA) were harvested from 89 patients undergoing coronary bypass surgery. Rings of these segments were exposed in organ bath experiments to metacholine (ME; 10 nmol/L -0.1 mmol/L) after precontraction with phenylephrine (PE; 10 µmol/L), and secondly to increasing concentrations of Ang II (0.1 nmol/L —1 µmol/L).

Results. Patients with the highest contraction to Ang II showed the lowest ME relaxation (r=0.312; p=0.003). Angiotensin-converting enzyme (ACE)-inhibition significantly increased Ang II sensitivity (p=0.03). This increase was accompanied by a tendency toward decreased EDR (p=0.07). The inverse relation between Ang responsiveness and endotheliumdependent relaxation could not be explained by an increased tissue or serum ACE-inhibition in patients with a higher endothelium-dependent relaxation.

Conclusions. High Ang II responsiveness inversely correlates to EDR in IMA's of patients with established coronary artery disease. Short-term treatment with an ACE-inhibitor increased the response to Ang II, but had an adverse effect on EDR.

Key Words: Angiotensin II • Endothelial dysfunction • Human arteries • ACE-inhibition

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 6, No. 3, 145-150 (2005)
DOI: 10.3317/jraas.2005.021


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Voors, A. A Articles by van Gilst, W. H Search for Related Content PubMed PubMed Citation Articles by Voors, A. A Articles by van Gilst, W. H Social Bookmarking                         What's this?