Hypotension in transgenic mice expressing atrial natriuretic factor fusion genes.

Abstract

Chronic regulation of the cardiovascular system by atrial natriuretic factor was investigated by generating transgenic mice with elevated hormone levels in the systemic circulation. A fusion gene comprising the mouse transthyretin promoter and mouse atrial natriuretic factor structural sequences was designed so as to target hormone expression to the liver. Hepatic expression of atrial natriuretic factor was detectable as early as embryonic day 15 in transgenic animals. In adult transgenic mice, plasma immunoreactive atrial natriuretic factor concentration was elevated at least eightfold as compared with nontransgenic littermates. The mean arterial pressure of conscious transgenic mice was 75.5 ±0.9 mm Hg, significantly less than that of nontransgenic siblings (103.9±2.0 mm Hg). This difference in mean arterial pressure was not accompanied by significant changes in several other physiological parameters, including heart rate, plasma and urinary electrolytes, water intake, and urine volume. This study demonstrates that a chronic elevation of plasma atrial natriuretic factor decreases arterial blood pressure without inducing diuresis and natriuresis in transgenic mice and also illustrates the value of the transgenic approach for the study of the cardiovascular system. (Hypertension 1990;16:301-307)

Atrial natriuretic peptide (ANP) gene promoter variant and increased susceptibility to early development of hypertension in humans

“…1,2 The gene encoding ANP, a cardiac hormone with natriuretic diuretic and vasodilatory properties, 3 has been shown to favour development of high BP levels in genetically manipulated animal models. 4,5 Similar results were obtained with the manipulation of NPRA (natriuretic peptide receptor type A) gene. 6 Furthermore, the efficacy of a regulatable ANP gene therapy for hypertension has been recently demonstrated.…”

“…In fact, ablation of ANP gene leads to a form of salt-sensitive hypertension, 4 whereas overexpression of ANP causes hypotension. 5 What this study adds: K A molecular variant of ANP gene, which falls within the promoter region and has been previously associated to reduced NT-proANP plasma levels, 10 is associated with significantly higher blood pressure levels and with an increased prevalence of hypertension in young male subjects. K Carriers of the ANP gene promoter allelic variant show an increased predisposition to develop hypertension along with an increased occurrence of transitory cerebrovascular ischemic events over a 28-year follow-up period.…”

Cloning, Sequencing, and Enzymatic Activity of an Inducible Aldo-Keto Reductase from Chinese Hamster Ovary Cells

“…The polyacrylamide gel-purified riboprobe (0.5 ϫ 10 6 cpm) and tissue RNA (20 g) or CHO-K1 cell-derived RNA (2-5 g) were denatured at 85°C for 10 min and annealed overnight at 55°C in hybridization buffer (80% formamide, 40 mM PIPES, pH 6.5, 0.4 M NaCl, 1 mM EDTA). Sample processing and display were as described previously except that the ribonuclease digestion buffer contained 50 g/ml RNase A in addition to 2 g/ml RNase T1 (14).…”

The Regulation and Physiological Roles of the Guanylyl Cyclase Receptors.

“…Gene deletion of murine GC-A, GC-C, ANP, BNP, and CNP along with transgenic over-expression of ANP and BNP have pointed to some of the fundamental roles of these receptors and ligands in murine physiology [168][169][170][171][172][173][174][175][176].…”

“…ANP transgenic mice with a fusion construct consisting of the murine transthyretin promoter and murine ANP gene exhibit about a 30-mmHg decrease of systolic blood pressure [175]. ANP transgenic mice show 27% reduction in the heart weight and 21% reduction in the total peripheral resistance compared with wild-type mice [186].…”