Matsumura Y, Fujita K, Miyazaki Y, Takaoka M, Morimoto S
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S456-8.
The role of endothelin-1 (ET-1) in the development and maintenance of hypertension is controversial. To determine the role of ET-1, we investigated the possible involvement of ET-1 in the pathogenesis of experimental hypertensive rats. In deoxycorticosterone acetate (DOCA)-salt hypertensive rats, a significant increase in aortic immunoreactive ET (IR-ET) level was observed, compared with age-matched sham-operated rats. Intravenous injection of the ETA receptor antagonist FR139317 (10 mg/kg) produced a slight decrease in blood pressure in sham rats. In the DOCA-salt hypertensive rats, FR139317 had a more pronounced hypotensive effect. Treatment with the antagonist in nitro-L-arginine (LNA)-induced hypertensive rats, two-kidney, one-clip (2K1C) renal hypertensive rats, spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHR-SP) produced only moderate hypotensive effects, of the same degree as those in normotensive rats. Long-term treatment with FR139317 in DOCA-salt hypertensive rats efficiently suppressed the development of hypertension and cardiovascular hypertrophy. We propose that ET-1 production in vascular tissues is increased in DOCA-salt hypertensive rats. In addition, our study suggests the pathophysiologic importance of ET-1 and the ETA receptor in DOCA-salt-induced hypertension but not in SHR, in SHR-SP, in 2K1C renal hypertension, and in LNA-induced hypertension.
内皮素-1（ET-1）在高血压的发生和维持过程中的作用存在争议。为了确定ET-1的作用，我们研究了ET-1在实验性高血压大鼠发病机制中可能的参与情况。在醋酸脱氧皮质酮（DOCA）-盐性高血压大鼠中，与年龄匹配的假手术大鼠相比，观察到主动脉免疫反应性ET（IR-ET）水平显著升高。静脉注射ETA受体拮抗剂FR139317（10mg/kg）可使假手术大鼠的血压略有下降。在DOCA-盐性高血压大鼠中，FR139317具有更明显的降压作用。在硝基-L-精氨酸（LNA）诱导的高血压大鼠、二肾一夹（2K1C）肾性高血压大鼠、自发性高血压大鼠（SHR）和易卒中型SHR（SHR-SP）中，用该拮抗剂治疗仅产生中等程度的降压作用，与正常血压大鼠的降压程度相同。在DOCA-盐性高血压大鼠中，长期用FR139317治疗可有效抑制高血压的发展和心血管肥大。我们提出，DOCA-盐性高血压大鼠血管组织中ET-1的产生增加。此外，我们的研究表明，ET-1和ETA受体在DOCA-盐诱导的高血压中具有病理生理学重要性，但在SHR、SHR-SP、2K1C肾性高血压和LNA诱导的高血压中并非如此。
