Yasujima M, Abe K, Kanazawa M, Yoshida K, Kohzuki M, Sato M, Takeuchi K, Omata K, Tsunoda K, Kudo K
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Tohoku J Exp Med. 1989 May;158(1):85-94. doi: 10.1620/tjem.158.85.
To determine whether pharmacological control of blood pressure could affect the renal function and levels of atrial natriuretic polypeptide (ANP) in spontaneously hypertensive rats (SHR) with renal ablation, and to ascertain the benefits of antihypertensive drugs, we studied effects of oral administration of captopril (50 mg/kg/day), an inhibitor of angiotensin converting enzyme, benidipine (3 mg/kg/day) and nilvadipine (10 mg/kg/day), newly developed blockers of calcium channel, and indapamide (10 mg/kg/day) for 14 days on systolic blood pressure, serum creatinine, blood urea nitrogen, and plasma ANP concentration in SHR subjected to surgical removal of the left kidney and infarction of two-thirds of the right kidney (5/6 nephrectomy) a week before. Three weeks after the surgery, systolic blood pressure (mmHg) in the untreated group was 253 +/- 9 (n = 10), in the captopril group 156 +/- 9 (n = 7, p less than 0.05), in the benidipine group 197 +/- 9 (n = 7, p less than 0.05), in the nilvadipine group 146 +/- 9 (n = 7, p less than 0.05) and in the indapamide group 206 +/- 5 (n = 7, p less than 0.05). Serum creatinine (mg/100 ml) was lower in the captopril group (0.58 +/- 0.02, n = 7, p less than 0.05) and in the benidipine group (0.50 +/- 0.03, n = 7, p less than 0.05) but not in the nilvadipine group and in the indapamide group 3 weeks after 5/6 nephrectomy compared to the untreated group. Blood urea nitrogen was also lower in the captopril group and in the benidipine group but not in the nilvadipine group and in the indapamide group. Plasma ANP concentration was significantly reduced by the treatment with captopril and benidipine but not with nilvadipine and indapamide. These results suggest that the reduction of blood pressure by the inhibition of angiotensin converting enzyme with captopril has the potential to ameliorate renal function of the SHR with remnant kidney, a model of chronic renal failure with hypertension, associated with the decreased concentration of plasma ANP. However, it remains to be determined whether the reduction of blood pressure by calcium channel blockers may be involved in the delayed progression of renal failure in this model since there were disparate effects on renal function and plasma ANP concentration with these two calcium channel blockers.
为了确定血压的药物控制是否会影响肾切除的自发性高血压大鼠（SHR）的肾功能和心房利钠多肽（ANP）水平，并确定抗高血压药物的益处，我们研究了口服血管紧张素转换酶抑制剂卡托普利（50毫克/千克/天）、新开发的钙通道阻滞剂贝尼地平（3毫克/千克/天）和尼伐地平（10毫克/千克/天）以及吲达帕胺（10毫克/千克/天）14天对一周前接受左肾手术切除和右肾三分之二梗死（5/6肾切除）的SHR的收缩压、血清肌酐、血尿素氮和血浆ANP浓度的影响。手术后三周，未治疗组的收缩压（mmHg）为253±9（n = 10），卡托普利组为156±9（n = 7，p<0.05），贝尼地平组为197±9（n = 7，p<0.05），尼伐地平组为146±9（n = 7，p<0.05），吲达帕胺组为206±5（n = 7，p<0.05）。与未治疗组相比，5/6肾切除术后三周，卡托普利组（0.58±0.02，n = 7，p<0.05）和贝尼地平组（0.50±0.03，n = 7，p<0.05）的血清肌酐（毫克/100毫升）较低，但尼伐地平组和吲达帕胺组没有降低。卡托普利组和贝尼地平组的血尿素氮也较低，但尼伐地平组和吲达帕胺组没有降低。卡托普利和贝尼地平治疗可显著降低血浆ANP浓度，但尼伐地平和吲达帕胺则无此作用。这些结果表明，用卡托普利抑制血管紧张素转换酶来降低血压有可能改善残余肾SHR的肾功能，残余肾SHR是一种伴有高血压的慢性肾衰竭模型，与血浆ANP浓度降低有关。然而，由于这两种钙通道阻滞剂对肾功能和血浆ANP浓度有不同影响，钙通道阻滞剂降低血压是否可能参与该模型中肾衰竭的延迟进展仍有待确定。
