Symons J D, Stebbins C L, Musch T I
Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, Davis, California 95616, USA.
J Appl Physiol (1985). 1999 Aug;87(2):574-81. doi: 10.1152/jappl.1999.87.2.574.
We hypothesized that nitric oxide (NO) opposes ANG II-induced increases in arterial pressure and reductions in renal, splanchnic, and skeletal muscle vascular conductance during dynamic exercise in normal and heart failure rats. Regional blood flow and vascular conductance were measured during treadmill running before (unblocked exercise) and after 1) ANG II AT(1)-receptor blockade (losartan, 20 mg/kg ia), 2) NO synthase (NOS) inhibition [N(G)-nitro-L-arginine methyl ester (L-NAME); 10 mg/kg ia], or 3) ANG II AT(1)-receptor blockade + NOS inhibition (combined blockade). Renal conductance during unblocked exercise (4.79 +/- 0.31 ml x 100 g(-1) x min(-1) x mmHg(-1)) was increased after ANG II AT(1)-receptor blockade (6.53 +/- 0.51 ml x 100 g(-1) x min(-1) x mmHg(-1)) and decreased by NOS inhibition (2.12 +/- 0.20 ml x 100 g(-1) x min(-1) x mmHg(-1)) and combined inhibition (3.96 +/- 0.57 ml x 100 g(-1) x min(-1) x mmHg(-1); all P < 0.05 vs. unblocked). In heart failure rats, renal conductance during unblocked exercise (5.50 +/- 0.66 ml x 100 g(-1) x min(-1) x mmHg(-1)) was increased by ANG II AT(1)-receptor blockade (8.48 +/- 0.83 ml x 100 g(-1) x min(-1) x mmHg(-1)) and decreased by NOS inhibition (2.68 +/- 0.22 ml x 100 g(-1) x min(-1) x mmHg(-1); both P < 0.05 vs. unblocked), but it was unaltered during combined inhibition (4.65 +/- 0.51 ml x 100 g(-1) x min(-1) x mmHg(-1)). Because our findings during combined blockade could be predicted from the independent actions of NO and ANG II, no interaction was apparent between these two substances in control or heart failure animals. In skeletal muscle, L-NAME-induced reductions in conductance, compared with unblocked exercise (P < 0.05), were abolished during combined inhibition in heart failure but not in control rats. These observations suggest that ANG II causes vasoconstriction in skeletal muscle that is masked by NO-evoked dilation in animals with heart failure. Because reductions in vascular conductance between unblocked exercise and combined inhibition were less than would be predicted from the independent actions of NO and ANG II, an interaction exists between these two substances in heart failure rats. L-NAME-induced increases in arterial pressure during treadmill running were attenuated (P < 0.05) similarly in both groups by combined inhibition. These findings indicate that NO opposes ANG II-induced increases in arterial pressure and in renal and skeletal muscle resistance during dynamic exercise.
我们假设，在正常和心力衰竭大鼠的动态运动过程中，一氧化氮（NO）可对抗血管紧张素II（ANG II）引起的动脉血压升高以及肾、内脏和骨骼肌血管传导性降低。在跑步机跑步期间，于以下情况之前（无阻断运动）和之后测量局部血流量和血管传导性：1）ANG II 1型受体阻断（氯沙坦，20 mg/kg腹腔注射）、2）一氧化氮合酶（NOS）抑制[N-硝基-L-精氨酸甲酯（L-NAME）；10 mg/kg腹腔注射]或3）ANG II 1型受体阻断+NOS抑制（联合阻断）。无阻断运动期间的肾传导性（4.79±0.31 ml×100 g⁻¹×min⁻¹×mmHg⁻¹）在ANG II 1型受体阻断后升高（6.53±0.51 ml×100 g⁻¹×min⁻¹×mmHg⁻¹），而在NOS抑制后降低（2.12±0.20 ml×100 g⁻¹×min⁻¹×mmHg⁻¹），联合抑制时降低（3.96±0.57 ml×100 g⁻¹×min⁻¹×mmHg⁻¹；与无阻断相比，所有P<0.05）。在心力衰竭大鼠中，无阻断运动期间的肾传导性（5.50±0.66 ml×100 g⁻¹×min⁻¹×mmHg⁻¹）在ANG II 1型受体阻断后升高（8.48±0.83 ml×100 g⁻¹×min⁻¹×mmHg⁻¹），在NOS抑制后降低（2.68±0.22 ml×100 g⁻¹×min⁻¹×mmHg⁻¹；与无阻断相比，两者P<0.05），但在联合抑制期间未改变（4.65±0.51 ml×100 g⁻¹×min⁻¹×mmHg⁻¹）。由于联合阻断期间我们的发现可从NO和ANG II的独立作用预测，在对照或心力衰竭动物中这两种物质之间未观察到明显相互作用。在骨骼肌中，与无阻断运动相比，L-NAME引起的传导性降低（P<0.05）在心力衰竭大鼠联合抑制期间被消除，但在对照大鼠中未被消除。这些观察结果表明，ANG II在心力衰竭动物中引起骨骼肌血管收缩，但被NO引起的扩张所掩盖。由于无阻断运动与联合抑制之间血管传导性的降低小于从NO和ANG II的独立作用所预测的值，在心力衰竭大鼠中这两种物质之间存在相互作用。联合抑制使两组在跑步机跑步期间L-NAME引起的动脉血压升高均类似地减弱（P<0.05）。这些发现表明，在动态运动期间，NO可对抗ANG II引起的动脉血压升高以及肾和骨骼肌阻力增加。
