Rankin A J, Swift F V
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Pflugers Arch. 1990 Dec;417(4):353-9. doi: 10.1007/BF00370652.
This study was designed to investigate whether atrial natriuretic factor (ANF) administered over the physiological, pathological and pharmacological range has a negative inotropic action on the heart. Anesthetized rabbits were infused with increasing doses of ANF (0.05, 0.25 and 0.5 micrograms kg-1 min-1), while measuring hemodynamic variables including the maximum rate of change of left ventricular pressure (dP/dtmax) as an index of inotropic state. Plasma levels of immunoreactive ANF (iANF) were measured to relate the hemodynamic changes to actual plasma levels of the peptide. Administration of ANF was associated with decreases in blood pressure, left ventricular pressure and dP/dtmax so that after 0.5 micrograms kg-1 min-1 infusion, these variables had decreased by 21 +/- 2 mmHg, 21 +/- 5.3 mmHg and 925 +/- 175 mmHg/s, respectively (P less than 0.01). There were no significant changes in right atrial pressure, left ventricular end-diastolic pressure or heart rate. Since dP/dtmax can be influenced by changing hemodynamic variables and baroreflex changes, a second group of rabbits was studied in which afterload and heart rate were held artificially constant. Again, in this group of rabbits, infusions of AFN led to decreasing inotropic state, so that at the highest infusion rate, a 14% decrease in dP/dtmax was observed (P less than 0.05). By comparison, hydralazine, a drug which causes active vasodilatation but no direct inotropic action, significantly (P less than 0.01) decreased blood pressure, left ventricular pressure and dP/dtmax when infused at a rate of 10 micrograms kg-1 min-1. However, in animals in which afterload was controlled, hydralazine did not affect any of the variables measured.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究旨在调查在生理、病理和药理范围内给予心房利钠因子（ANF）是否对心脏有负性肌力作用。给麻醉的兔子输注递增剂量的ANF（0.05、0.25和0.5微克·千克⁻¹·分钟⁻¹），同时测量包括左心室压力最大变化率（dP/dtmax）在内的血流动力学变量，以作为肌力状态的指标。测量免疫反应性ANF（iANF）的血浆水平，以将血流动力学变化与该肽的实际血浆水平相关联。给予ANF与血压、左心室压力和dP/dtmax降低有关，因此在输注0.5微克·千克⁻¹·分钟⁻¹后，这些变量分别降低了21±2 mmHg、21±5.3 mmHg和925±175 mmHg/s（P<0.01）。右心房压力、左心室舒张末期压力或心率无显著变化。由于dP/dtmax可能受血流动力学变量变化和压力感受器反射变化的影响，因此对第二组兔子进行了研究，在该组中后负荷和心率被人为保持恒定。同样，在这组兔子中，输注AFN导致肌力状态降低，因此在最高输注速率下，观察到dP/dtmax降低了14%（P<0.05）。相比之下，肼屈嗪是一种引起主动血管舒张但无直接肌力作用的药物，当以10微克·千克⁻¹·分钟⁻¹的速率输注时，显著（P<0.01）降低了血压、左心室压力和dP/dtmax。然而，在控制了后负荷的动物中，肼屈嗪不影响任何测量变量。（摘要截短于250字）
