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Endothelium‐dependent regulation of arterial blood pressure by ANP: role of endogenous vasoactive endothelial factors
Author(s) -
Kuhn Michaela,
Kruse Markus N.,
Sabrane Karim
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a313-d
Subject(s) - endothelium , medicine , atrial natriuretic peptide , endocrinology , endothelins , nitric oxide , vascular permeability , endogeny , endothelin receptor , hypervolemia , blood pressure , autocrine signalling , receptor , blood volume
Atrial natriuretic peptide (ANP) 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 is controversial. To dissect the endothelium ‐ mediated actions of ANP in vivo , we recently inactivated the GC‐A gene selectively in endothelial cells by homologous loxP/Tie2‐Cre‐mediated recombination. Notably, mice with endothelial‐restricted GC‐A deletion (EC GC‐A KO mice) exhibit significant arterial hypertension, hypervolemia and cardiac hypertrophy. This hypervolemia is due to a diminished permeability of the microvascular endothelium to macromolecules such as albumin ( J Clin Invest 2005; 115 :). Published studies suggested that ANP not only modulates endothelial permeability, but also the endothelial synthesis/release of vasoactive factors such as endothelin‐1 (ET‐1) and nitric oxide (NO). Therefore, in the present study we investigated whether the chronic arterial hypertension of EC GC‐A KO mice is due to altered endogenous release and/or actions of ET‐1 and NO. Plasma and tissue levels of immunoreactive ET‐1 were not different in EC GC‐A KO and corresponding control mice. Even more, blood pressure responses to exogenous or endogenous ET‐1 as well as functional NO activity levels were not different between genotypes. This new genetic mouse model demonstrates that the vascular endothelium is critically involved in the hypovolemic and hypotensive effects of ANP. However, these effects are not mediated by ANP‐dependent alterations in the endothelial synthesis of ET‐1 or NO.