Vascular endothelium is critically involved in the hypotensive and hypovolemic actions of atrial natriuretic peptide

Karim Sabrane, Markus N. Kruse, Larissa Fabritz, Bernd Zetsche, Danuta Mitko, Boris V. Skryabin, Melanie Zwiener, Hideo A. Baba, Masashi Yanagisawa, Michaela Kuhn

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111 Citations (Scopus)

Abstract

Atrial natriuretic peptide (ANP), via its vasodilating and diuretic effects, has an important physiological role in the maintenance of arterial blood pressure and volume. Its guanylyl cyclase-A (GC-A) receptor is highly expressed in vascular endothelium, but the functional relevance of this is controversial. To dissect the endothelium-mediated actions of ANP in vivo, we inactivated the GC-A gene selectively in endothelial cells by homologous loxP/Tie2-Cre-mediated recombination. Notably, despite full preservation of the direct vasodilating effects of ANP, mice with endothelium-restricted deletion of the GC-A gene (EC GC-A KO) exhibited significant arterial hypertension and cardiac hypertrophy. Echocardiographic and Doppler flow evaluations together with the Evan's blue dilution technique showed that the total plasma volume of EC GC-A KO mice was increased by 11-13%, even under conditions of normal dietary salt intake. Infusion of ANP caused immediate increases in hematocrit in control but not in EC GC-A KO mice, which indicated that ablation of endothelial GC-A completely prevented the acute contraction of intravascular volume produced by ANP. Furthermore, intravenous ANP acutely enhanced the rate of clearance of radio-iodinated albumin from the circulatory system in control but not in EC GC-A KO mice. We conclude that GC-A-mediated increases in endothelial permeability are critically involved in the hypovolemic, hypotensive actions of ANP.

Original languageEnglish (US)
Pages (from-to)1666-1674
Number of pages9
JournalJournal of Clinical Investigation
Volume115
Issue number6
DOIs
StatePublished - Jun 2005

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Hypovolemia
Vascular Endothelium
Atrial Natriuretic Factor
Endothelium
atrial natriuretic factor receptor A
Indicator Dilution Techniques
Evans Blue
Plasma Volume
Cardiomegaly
Cardiovascular System
Blood Volume
Radio
Hematocrit
Diuretics
Genetic Recombination
Genes
Albumins
Permeability
Arterial Pressure
Endothelial Cells

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sabrane, K., Kruse, M. N., Fabritz, L., Zetsche, B., Mitko, D., Skryabin, B. V., ... Kuhn, M. (2005). Vascular endothelium is critically involved in the hypotensive and hypovolemic actions of atrial natriuretic peptide. Journal of Clinical Investigation, 115(6), 1666-1674. https://doi.org/10.1172/JCI23360

Vascular endothelium is critically involved in the hypotensive and hypovolemic actions of atrial natriuretic peptide. / Sabrane, Karim; Kruse, Markus N.; Fabritz, Larissa; Zetsche, Bernd; Mitko, Danuta; Skryabin, Boris V.; Zwiener, Melanie; Baba, Hideo A.; Yanagisawa, Masashi; Kuhn, Michaela.

In: Journal of Clinical Investigation, Vol. 115, No. 6, 06.2005, p. 1666-1674.

Research output: Contribution to journalArticle

Sabrane, K, Kruse, MN, Fabritz, L, Zetsche, B, Mitko, D, Skryabin, BV, Zwiener, M, Baba, HA, Yanagisawa, M & Kuhn, M 2005, 'Vascular endothelium is critically involved in the hypotensive and hypovolemic actions of atrial natriuretic peptide', Journal of Clinical Investigation, vol. 115, no. 6, pp. 1666-1674. https://doi.org/10.1172/JCI23360
Sabrane, Karim ; Kruse, Markus N. ; Fabritz, Larissa ; Zetsche, Bernd ; Mitko, Danuta ; Skryabin, Boris V. ; Zwiener, Melanie ; Baba, Hideo A. ; Yanagisawa, Masashi ; Kuhn, Michaela. / Vascular endothelium is critically involved in the hypotensive and hypovolemic actions of atrial natriuretic peptide. In: Journal of Clinical Investigation. 2005 ; Vol. 115, No. 6. pp. 1666-1674.
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