Ogawa K, Matsunaga M, Nagai H, Hara A, Koide H, Pak C H, Hirakawa A, Kawai C
Tohoku J Exp Med. 1985 Feb;145(2):125-35. doi: 10.1620/tjem.145.125.
The effects of enalapril maleate (MK-421), a new angiotensin converting enzyme inhibitor, were studied on 5 patients with renovascular hypertension (RVH) due to unilateral renal artery stenosis. The therapeutic dosage was increased when the blood pressure (BP) was not controlled for more than 3 days. Blood sampling was performed before, and 5 hr and 24 hr after the first administration, and on the 3rd day with each dosage. The BP was normalized on 5 mg/day in 1 case, 10 mg in 1 case, 20 mg in 2 cases, and 40 mg plus mefruside in 1 case. Plasma renin activity (PRA) was significantly increased after 5 hr and recovered after 24 hr with 2.5 mg of the enalapril maleate, when the BP was not affected. This indicates that the increase in PRA is likely due to the reduced negative feedback of angiotensin II. When the blood pressure was lowered, PRA was increased and plasma aldosterone concentration (PAC) was decreased significantly. This rise of PRA may depend not only on the reduced negative feedback but also on the fall of BP. It is also considered that the PAC was decreased through the decrease in plasma angiotensin II. A fall of the glomerular filtration rate in one case and also a fall of the perfusion of the kidney of the stenotic side in another case were observed by radioisotope renograms. MK-421 administration was a useful treatment for RVH, and clearly normalized the BP of all the patients studied. However, there was a risk of a fall of renal function on the stenotic side due to the decrease in perfusion pressure.
对5例因单侧肾动脉狭窄所致肾血管性高血压(RVH)患者研究了新型血管紧张素转换酶抑制剂马来酸依那普利(MK - 421)的效果。若血压(BP)在3天以上未得到控制,则增加治疗剂量。在首次给药前、给药后5小时和24小时以及每种剂量给药的第3天进行血样采集。1例患者服用5mg/天、1例服用10mg/天、2例服用20mg/天以及1例服用40mg加味塞米后血压恢复正常。服用2.5mg马来酸依那普利后,血压未受影响时,血浆肾素活性(PRA)在5小时后显著升高,并在24小时后恢复。这表明PRA升高可能是由于血管紧张素II的负反馈减少所致。当血压降低时,PRA升高,血浆醛固酮浓度(PAC)显著降低。PRA的这种升高可能不仅取决于负反馈减少,还取决于血压下降。还认为PAC是通过血浆血管紧张素II的减少而降低的。通过放射性同位素肾图观察到1例患者肾小球滤过率下降,另1例患者狭窄侧肾脏灌注下降。服用MK - 421是治疗RVH的有效方法,且明显使所有研究患者的血压恢复正常。然而,由于灌注压降低,存在狭窄侧肾功能下降的风险。