Engineering the cardiovascular system. Blood pressure regulation

M. E. Steinhelper, K. L. Cochrane, Loren Field

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We have generated several lineages of transgenic mice that exhibit chronic elevations in the steady-state concentration of atrial natriuretic factor (ANF) in the peripheral circulation. ANF, a peptide hormone synthesized primarily by atrial cardiomyocytes, is a potent natriuretic and diuretic. ANF also reduces blood pressure transiently when acutely administered. To address the potential role of ANF in chronic cardiovascular regulation, we generated transgenic mice that express the ANF gene in the liver. The fusion genes comprised either the mouse transthyretin (TTR) or rat phosphoenolpyruvate carboxykinase (PEPCK) promoters fused to the mouse ANF structural gene and were designed to target to the liver constitutive and inducible expression of pre-pro-ANF, respectively. Transgenic animals harboring the TTR-ANF fusion gene expressed chimeric ANF transcripts exclusively in the liver. In contrast, mice harboring the PEPCK-ANF fusion gene did not express detectable amounts of ANF mRNA in liver even after induction (24-hour fasting). In the TTR-ANF mice, hepatic and plasma immunoreactive ANF concentrations were proportional to the concentration of hepatic ANF transcripts. Moreover, mean arterial blood pressure recorded in conscious transgenic mice was inversely proportional to hepatic ANF expression. These transgenic models demonstrate that chronically elevated ANF concentration can induce sustained hypotension.

Original languageEnglish
Pages (from-to)248-253
Number of pages6
JournalAnnals of the New York Academy of Sciences
Volume646
StatePublished - 1991
Externally publishedYes

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Pressure regulation
Cardiovascular system
Blood pressure
Atrial Natriuretic Factor
Cardiovascular System
Blood Pressure
Liver
Genes
Prealbumin
Gene Fusion
Transgenic Mice
Phosphoenolpyruvate
Fusion reactions
Gene
Mouse
Arterial Pressure
Fusion
Genetically Modified Animals

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Engineering the cardiovascular system. Blood pressure regulation. / Steinhelper, M. E.; Cochrane, K. L.; Field, Loren.

In: Annals of the New York Academy of Sciences, Vol. 646, 1991, p. 248-253.

Research output: Contribution to journalArticle

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