Ohte N, Cheng C P, Suzuki M, Little W C
Section of Cardiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
J Pharmacol Exp Ther. 1999 Nov;291(2):589-95.
Atrial natriuretic peptide (ANP) has potent vasodilatory and natriuretic actions and may have therapeutic benefit in congestive heart failure (CHF). These benefits may be offset by a negative inotropic effect of ANP seen in isolated preparations. However, ANP's integrated effect on left ventricular (LV) contraction and relaxation, independent of loading conditions, both under normal conditions and after CHF, is not known. We studied six conscious dogs, instrumented to measure LV and left atrial pressures and to determine LV volume from three dimensions. ANP produced significant (P<.05) decreases in LV end-systolic pressure (101.2+/-11.8 versus 91.7+/-11.2 mm Hg, P<.05) in normal dogs and in dogs with CHF (93.1+/-6.4 versus 87.1+/- 4.4 mm Hg, P<.05). ANP also caused significant reductions of the slope of end-systolic pressure-end-systolic volume relation both before (7.0 +/-1.5 versus 6.3+/-1.5 mm Hg/ml) and after CHF (4.8+/-1.3 versus 4.4+/-1.2 mm Hg/ml, P<.05). Both before and after CHF, ANP slowed LV relaxation at matched end-systolic pressure. Before CHF, steady-state stroke volume and peak LV filling rate (dV/dt(max)) were reduced. However, after CHF, the fall in end-systolic pressure more than offset the load-independent LV depression, as stroke volume, the rate LV relaxation, and dV/dt(max) were increased and minimum LV pressure reduced. ANP has negative effects on LV contractility and relaxation both before and after CHF. However, after CHF, afterload reduction with ANP overcomes its negative effects, resulting in net improvement of LV ejection and relaxation. Thus, the direct cardiodepressant effects of ANP should not limit its usefulness in CHF.
心房利钠肽（ANP）具有强大的血管舒张和利钠作用，可能对充血性心力衰竭（CHF）具有治疗益处。在离体标本中观察到的ANP负性肌力作用可能会抵消这些益处。然而，在正常条件下以及CHF后，ANP对左心室（LV）收缩和舒张的综合作用（独立于负荷条件）尚不清楚。我们研究了6只清醒犬，通过仪器测量LV和左心房压力，并从三维角度确定LV容积。在正常犬和CHF犬中，ANP均使LV收缩末期压力显著降低（P<0.05）（正常犬：101.2±11.8 vs 91.7±11.2 mmHg，P<0.05；CHF犬：93.1±6.4 vs 87.1±4.4 mmHg，P<0.05）。ANP还使收缩末期压力-收缩末期容积关系的斜率在CHF前后均显著降低（CHF前：7.0±1.5 vs 6.3±1.5 mmHg/ml；CHF后：4.8±1.3 vs 4.4±1.2 mmHg/ml，P<0.05）。在CHF前后，在匹配的收缩末期压力下，ANP均减慢了LV舒张。CHF前，稳态搏出量和LV最大充盈率（dV/dt(max)）降低。然而，CHF后，收缩末期压力的下降超过了负荷无关的LV抑制作用，因为搏出量、LV舒张速率和dV/dt(max)增加，LV最小压力降低。ANP在CHF前后对LV收缩性和舒张均有负面影响。然而，CHF后，ANP降低后负荷克服了其负面影响，导致LV射血和舒张得到净改善。因此，ANP的直接心脏抑制作用不应限制其在CHF中的应用。
