Cardiovascular effects of chronic high-dose atriopeptin III infusion in normotensive rats

Seventy-eight Sprague-Dawley rats received continuous intravenous infusions of either atriopeptin III (APIII), 60 micrograms/kg/hr, or distilled water vehicle for a period of 7 days by means of osmotic minipumps. On Day 7 approximately one-half of the animals (20 vehicle-treated rats and 21 APIII-treated rats) were instrumented for evaluation of cardiac function and terminated for measurement of heart weight. The minipumps remained in place during the evaluation of cardiac function. Also on Day 7, the osmotic pumps were removed from the remaining animals and an additional 7 days were allowed to elapse before heart weight and cardiac function were evaluated. Mean arterial blood pressure (MAP) of rats receiving APIII for 7 days was significantly lower (-9%, p less than 0.05) than that of rats receiving vehicle for 7 days. In addition, reductions (p less than 0.05) of total ventricular weightdry (-7%), left ventricular weightdry (-8%), and right ventricular weightdry (-9%) were observed in the APIII-treated rats (all ventricular weights are normalized for body weight). Hematocrit (HCT) was significantly higher (13%, p less than 0.05) in the APIII-treated group. Chronic APIII infusion did not influence ventricular performance nor did it affect regional vascular resistances. Seven days after termination of the APIII infusion the differences in MAP and HCT between vehicle-treated and APIII-treated animals were no longer evident. Partial recovery of the effect on heart weights was apparent, with total ventricular weightdry and left ventricular weightdry remaining slightly reduced (-4 and -5%, respectively; p less than 0.05). No differences were found between the two recovery groups for any index of cardiac function. In separate experiments, it was demonstrated that APIII, 60 micrograms/kg/hr iv, caused a significant increase in urine volume (p less than 0.05 relative to vehicle) during the initial 24 hr of infusion. The results indicate that chronic infusion of a large diuretic dose of APIII exerts relatively little influence on overall cardiovascular function in normotensive rats.