Sakai S, Miyauchi T, Hara J, Goto K, Yamaguchi I
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
J Cardiovasc Pharmacol. 2000 Nov;36(5 Suppl 1):S95-8. doi: 10.1097/00005344-200036051-00031.
The pharmacological characterization of endothelin-1 (ET-1) in the pulmonary circulation in pulmonary hypertension (PH) is not known precisely. We investigated the effect of intravenous injection of ET-1 (1000 pmol/kg) on right ventricular systolic pressure (RVSP) (which is equal to systolic pulmonary arterial pressure) in rats with monocrotaline-induced PH. ET-1 decreased RVSP in PH rats; however, ET-1 did not alter RVSP in control rats, suggesting that ET-1 causes dilatation of the pulmonary artery in PH rats. Under pretreatment with the endothelin-A- (ET(A)) receptor antagonist BMS 193884, ET-1 decreased RVSP in PH rats more than in control rats, suggesting that pulmonary vasodilator action of ET-I mediated via the ET(B)-receptor pathway is augmented in PH rats. Under pretreatment with the ET(A/B)-receptor antagonist SB 209670, the effect of ET-1 in lowering pulmonary arterial pressure was abolished in both groups of rats. These results suggest that the hypotensive effect of ET-1 on pulmonary circulation mediated via the ET(B)-receptor pathway is enhanced in PH rats compared with control normal rats. It is considered that the blockade of only the ET(A)-receptor pathway is preferable to the blockade of both the ET(A)- and ET(B)-receptor pathways in the treatment of PH.
内皮素-1（ET-1）在肺动脉高压（PH）患者肺循环中的药理学特性尚不完全清楚。我们研究了静脉注射ET-1（1000 pmol/kg）对用野百合碱诱导的PH大鼠右心室收缩压（RVSP，等同于收缩期肺动脉压）的影响。ET-1可降低PH大鼠的RVSP；然而，ET-1对对照大鼠的RVSP无影响，提示ET-1可使PH大鼠的肺动脉扩张。在用内皮素-A（ET(A)）受体拮抗剂BMS 193884预处理后，ET-1降低PH大鼠RVSP的作用比对照大鼠更明显，提示在PH大鼠中，ET-1通过ET(B)受体途径介导的肺血管舒张作用增强。在用ET(A/B)受体拮抗剂SB 209670预处理后，两组大鼠中ET-1降低肺动脉压的作用均被消除。这些结果提示，与对照正常大鼠相比，在PH大鼠中，ET-1通过ET(B)受体途径介导的对肺循环的降压作用增强。在PH治疗中，仅阻断ET(A)受体途径优于同时阻断ET(A)和ET(B)受体途径。
