Moreau N, Richer C, Vincent M P, Giudicelli J F
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
J Cardiovasc Pharmacol. 1993 Jul;22(1):126-34. doi: 10.1097/00005344-199307000-00020.
Nonselective inhibition of endogenous angiotensin II (AII) by AI-converting enzyme inhibitors (ACEI) results in sympathoinhibitory effects. We wished to examine the influence of selective inhibition of endogenous AII by losartan, a nonpeptide AT1-receptor antagonist, on the sympathetic system. Cardiac, systemic, and regional vascular (kidney, mesentery, hindlimb) responses to selective alpha 1- and alpha 2-adrenoceptor agonists and to electrical stimulation of the spinal cord were investigated in pithed spontaneously hypertensive rats (SHR) by pulsed Doppler technique. Losartan (10 mg/kg) was administered orally, either as a single dose or for 8 successive days. Under both conditions, AII systemic pressor, regional vasoconstrictor, and tachycardic responses were completely abolished by losartan. At the vascular level, losartan did not affect postsynaptic alpha 1-adrenoceptor-mediated systemic pressor and regional vasconstrictor responses, but reduced postsynaptic alpha 2-adrenoceptor-mediated renal vasoconstriction. Losartan significantly decreased the systemic pressor and regional vasoconstrictor responses elicited by spinal cord stimulation. This sympathoinhibitory effect was not homogeneously distributed, preferentially affecting the kidney. At the cardiac level, spinal cord stimulation induced a strong tachycardia which remained unaffected by losartan. Thus in SHR, losartan exerts sympathoinhibitory effects against the vascular but not the cardiac responses to spinal cord stimulation. Because the vascular responses to postjunctional alpha 1- and alpha 2-adrenoceptor stimulation, except in the kidney, simultaneously remain poorly affected, the sympathoinhibitory effects of losartan mainly develop prejunctionally through AT1-receptors blockade.
血管紧张素转换酶抑制剂（ACEI）对内源性血管紧张素II（AII）的非选择性抑制会产生交感神经抑制作用。我们希望研究非肽类AT1受体拮抗剂氯沙坦对内源性AII的选择性抑制对交感神经系统的影响。采用脉冲多普勒技术，在脊髓横断的自发性高血压大鼠（SHR）中，研究了心脏、全身和局部血管（肾脏、肠系膜、后肢）对选择性α1和α2肾上腺素能受体激动剂以及脊髓电刺激的反应。氯沙坦（10mg/kg）以单剂量或连续8天口服给药。在这两种情况下，氯沙坦均可完全消除AII的全身升压、局部血管收缩和心动过速反应。在血管水平，氯沙坦不影响突触后α1肾上腺素能受体介导的全身升压和局部血管收缩反应，但可减弱突触后α2肾上腺素能受体介导的肾血管收缩。氯沙坦可显著降低脊髓刺激引起的全身升压和局部血管收缩反应。这种交感神经抑制作用分布不均一，优先影响肾脏。在心脏水平，脊髓刺激可诱发强烈的心动过速，氯沙坦对此无影响。因此，在SHR中，氯沙坦对脊髓刺激引起的血管反应具有交感神经抑制作用，但对心脏反应无影响。由于除肾脏外，对突触后α1和α2肾上腺素能受体刺激的血管反应同时仍受影响较小，氯沙坦的交感神经抑制作用主要通过阻断AT1受体在突触前发挥作用。
