Transgenic mice with lifelong ANF elevation exhibited a 24 mm Hg reduction in mean arterial pressure and a 21% reduction in total peripheral resistance compared to nontransgenic littermates.
Does lifelong overexpression of atrial natriuretic factor alter systemic and regional hemodynamics in mice?
Lifelong elevation of ANF in transgenic mice causes a chronic reduction in blood pressure driven by reduced total peripheral resistance, despite an increase in plasma volume.
The circulatory effects associated with lifelong plasma atrial natriuretic factor (ANF) elevation were examined by generating transgenic mice, which constitutively express a fusion gene consisting of the transthyretin promoter and the ANF structural gene. These mice have chronically elevated ANF levels as compared with their nontransgenic siblings. Transgenic animals exhibited immunoreactive ANF levels that were nearly fivefold higher than those measured in nontransgenic littermates. Systemic and regional hemodynamics and blood volumes were explored by using modifications of the reference microsphere and dilution techniques. Mean arterial pressure was reduced by 24 mm Hg, associated with a 27% reduction in total heart weight. This chronic reduction in blood pressure was due to a 21% reduction in total peripheral resistance, whereas cardiac output, stroke volume, and heart rate were not significantly altered, despite a 15% elevation in plasma volume. Transgenic mice displayed reductions of 35%, 33%, 32%, and 19% in muscle, skin, brain, and renal vascular resistance, respectively, whereas coronary and splanchnic resistances were not significantly altered. The findings complement earlier data from chronically infused normotensive mammals and suggest that these mice are an excellent model for investigating the effects of lifelong ANF elevation.
Barbee et al. (Fri,) conducted a other in Lifelong plasma atrial natriuretic factor (ANF) elevation. Transgenic overexpression of atrial natriuretic factor (ANF) vs. Nontransgenic siblings/littermates was evaluated on Systemic and regional hemodynamics and blood volumes. Transgenic mice with lifelong ANF elevation exhibited a 24 mm Hg reduction in mean arterial pressure and a 21% reduction in total peripheral resistance compared to nontransgenic littermates.