Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2014 Sep 29;9(9):e103909.
doi: 10.1371/journal.pone.0103909. eCollection 2014.

Statin treatment in hypercholesterolemic men does not attenuate angiotensin II-induced venoconstriction

Christoph Schindler  1 , Kristina Guenther  2 , Cosima Hermann  2 , Carlos M Ferrario  3 , Christoph Schroeder  4 , Sven Haufe  4 , Jens Jordan  4 , Wilhelm Kirch  2
Affiliations
Randomized Controlled Trial

Statin treatment in hypercholesterolemic men does not attenuate angiotensin II-induced venoconstriction

Christoph Schindler et al. PLoS One. .

Erratum in

  • PLoS One. 2014;9(10):e112205

Abstract

Experimental studies suggested that statins attenuate vascular AT1 receptor responsiveness. Moreover, the augmented excessive pressor response to systemic angiotensin II infusions in hypercholesterolemic patients was normalized with statin treatment. In 12 hypercholesterolemic patients, we tested the hypothesis that statin treatment attenuates angiotensin II-mediated vasoconstriction in hand veins assessed by a linear variable differential transducer. Subjects ingested daily doses of either atorvastatin (40 mg) or positive control irbesartan (150 mg) for 30 days in a randomized and cross-over fashion. Ang II-induced venoconstriction at minute 4 averaged 59%±10% before and 28%±9% after irbesartan (mean ± SEM; P<0.05) compared to 65%±11% before and 73%±11% after 30 days of atorvastatin treatment. Plasma angiotensin levels increased significantly after irbesartan treatment (Ang II: 17±22 before vs 52±40 pg/mL after [p = 0.048]; Ang-(1-7): 18±10 before vs 37±14 pg/mL after [p = 0.002]) compared to atorvastatin treatment (Ang II: 9±4 vs 11±10 pg/mL [p = 0.40]; Ang-(1-7): 24±9 vs 32±8 pg/mL [p = 0.023]). Our study suggests that statin treatment does not elicit major changes in angiotensin II-mediated venoconstriction or in circulating angiotensin II levels whereas angiotensin-(1-7) levels increased modestly. The discrepancy between local vascular and systemic angiotensin II responses might suggest that statin treatment interferes with blood pressure buffering reflexes.

Trial registration: ClinicalTrials.gov NCT00154024.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The study was supported by a restricted grant of Sanofi-Aventis. This does not alter the author's adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Consort Flow Diagram.
Figure 2
Figure 2. Atorvastatin and irbesartan influences on plasma concentrations of angiotensin II.
Within-group differences were analyzed with Students paired t-test and between-group differences with a two-way ANOVA. Data are expressed as individual values and as mean ± SEM.
Figure 3
Figure 3. Atorvastatin and irbesartan influences on plasma concentrations of angiotensin-(1–7).
Within-group differences were analyzed with Students paired t-test and between-group differences with a two-way ANOVA. Data are expressed as individual values and as mean ± SEM.
Figure 4
Figure 4. Time course of dorsal hand vein constriction with constant angiotensin II infusion.
Infusion rate: 50 ng/min over 24 minutes before (pre) and after (post) treatment with atorvastatin. Differences between pre- and post-treatment were analyzed with a two-way ANOVA with Bonferroni's post hoc tests to test for differences at single time points. Data are expressed as mean ± SEM.
Figure 5
Figure 5. Time course of dorsal hand vein constriction with constant angiotensin II infusion.
Infusion rate: 50 ng/min over 24 minutes before (pre) and after (post) treatment with irbesartan. Differences between pre- and post-treatment were analyzed with a two-way ANOVA with Bonferroni's post hoc tests to test for differences at single time points. Data are expressed as mean ± SEM.
Figure 6
Figure 6. Dilation of preconstricted dorsal hand veins elicited by incremental histamine infusions.
Between-group differences were analyzed with a two-way ANOVA. Data are expressed as mean ± SEM.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Nickenig G, Baumer AT, Temur Y, Kebben D, Jockenhovel F, et al. (1999) Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men. Circulation 100: 2131–2134. - PubMed
    1. Maczewski M, Maczewska J, Duda M (2008) Hypercholesterolaemia exacerbates ventricular remodelling after myocardial infarction in the rat: role of angiotensin II type 1 receptors. Br J Pharmacol 154: 1640–1648. - PMC - PubMed
    1. Strehlow K, Wassmann S, Bohm M, Nickenig G (2000) Angiotensin AT1 receptor over-expression in hypercholesterolaemia. Ann Med 32: 386–389. - PubMed
    1. Dechend R, Fiebler A, Lindschau C, Bischoff H, Muller D, et al. (2001) Modulating angiotensin II-induced inflammation by HMG Co-A reductase inhibition. Am J Hypertens 14: 55S–61S. - PubMed
    1. Sim JS, Dick JB, Struthers AD (2004) Statin therapy increases vascular sensitivity to angiotensin II in hypercholesterolaemic patients. J Renin Angiotensin Aldosterone Syst 5: 109–113. - PubMed

Publication types

MeSH terms

Substances

Associated data