TY - JOUR
T1 - Effects of benidipine, a calcium antagonist, on urinary kallikrein excretion and renal impairment in experimental diabetes
AU - Yoshida, Kazunori
AU - Kohzuki, Masahiro
AU - Yasujima, Minoru
AU - Kanazawa, Masayuki
AU - Abe, Keishi
PY - 1996
Y1 - 1996
N2 - Objective To assess the long-term effects of different antihypertensive agents on urinary protein excretion and kallikrein excretion in diabetic rats with renal impairment Methods Uninephrectomized streptozotocin diabetic Wistar-Kyoto rats were randomly assigned to receive vehicle, a calcium antagonist (benidipine) or an angiotensin converting enzyme inhibitor (captopril) for up to 12 weeks. Active kallikrein was determined by its kininogenase activity, and generated kinins were measured by radioimmunoassay. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin. Results Urinary protein excretion increased significantly in diabetic rats compared with non-diabetic rats. Urinary active kallikrein excretion was significantly reduced in diabetic rats, whereas urinary total kallikrein excretion was unchanged, resulting in a reduced percentage of active to total kallikrein compared with that in non-diabetic rats. Benidipine and captopril reduced blood pressure and attenuated the development of diabetic renal impairment in a similar manner. However, only benidipine attenuated the decreases in urinary active kallikrein excretion and the ratio of active to total kallikrein in diabetic rats. Conclusions Although pathophysiological relevance of impaired urinary kallikrein activation to the development of diabetic renal impairment remains to be determined, our result might suggest a new mechanism by which calcium antagonists protect the kidney from diabetic renal impairment.
AB - Objective To assess the long-term effects of different antihypertensive agents on urinary protein excretion and kallikrein excretion in diabetic rats with renal impairment Methods Uninephrectomized streptozotocin diabetic Wistar-Kyoto rats were randomly assigned to receive vehicle, a calcium antagonist (benidipine) or an angiotensin converting enzyme inhibitor (captopril) for up to 12 weeks. Active kallikrein was determined by its kininogenase activity, and generated kinins were measured by radioimmunoassay. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin. Results Urinary protein excretion increased significantly in diabetic rats compared with non-diabetic rats. Urinary active kallikrein excretion was significantly reduced in diabetic rats, whereas urinary total kallikrein excretion was unchanged, resulting in a reduced percentage of active to total kallikrein compared with that in non-diabetic rats. Benidipine and captopril reduced blood pressure and attenuated the development of diabetic renal impairment in a similar manner. However, only benidipine attenuated the decreases in urinary active kallikrein excretion and the ratio of active to total kallikrein in diabetic rats. Conclusions Although pathophysiological relevance of impaired urinary kallikrein activation to the development of diabetic renal impairment remains to be determined, our result might suggest a new mechanism by which calcium antagonists protect the kidney from diabetic renal impairment.
KW - Angiotensin converting enzyme inhibitor
KW - Calcium antagonist
KW - Diabetes mellitus
KW - Kallikrein
KW - Kinin
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U2 - 10.1097/00004872-199602000-00010
DO - 10.1097/00004872-199602000-00010
M3 - Article
C2 - 8728299
AN - SCOPUS:0029925828
VL - 14
SP - 215
EP - 222
JO - Journal of Hypertension
JF - Journal of Hypertension
SN - 0263-6352
IS - 2
ER -