HEMODYNAMICS IN TRANSGENIC MICE WITH OVEREXPRESSION OF ATRIAL-NATRIURETIC-FACTOR

The circulatory effects associated with lifelong plasma atrial natriur etic factor (ANF) elevation were examined by generating transgenic mic e, which constitutively express a fusion gene consisting of the transt hyretin promoter and the ANF structural gene. These mice have chronica lly elevated ANF levels as compared with their nontransgenic siblings. Transgenic animals exhibited immunoreactive ANF levels that were near ly fivefold higher than those measured in nontransgenic littermates. S ystemic and regional hemodynamics and blood volumes were explored by u sing modifications of the reference microsphere and dilution technique s. Mean arterial pressure was reduced by 24 mm Hg, associated with a 2 7% reduction in total heart weight. This chronic reduction in blood pr essure was due to a 21% reduction in total peripheral resistance, wher eas cardiac output, stroke volume, and heart rate were not significant ly 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 spl anchnic resistances were not significantly altered. The findings compl ement earlier data from chronically infused normotensive mammals and s uggest that these mice are an excellent model for investigating the ef fects of lifelong ANF elevation.