Raje R, Ahmad S
Department of Pharmacology, Toxicology and Medicinal Chemistry, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University Brooklyn, New York, USA.
Clin Exp Hypertens. 1999 Jan-Feb;21(1-2):37-49. doi: 10.3109/10641969909068647.
Recently, we have shown that chronic administration of N-Nitro-L-Arginine Methyl Ester (L-NAME, an inhibitor of nitric oxide synthase) precipitates stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Angiotensin receptor antagonist (L-158,809) was shown to delay the onset of such stroke. In the present study, five groups of 4-week-old SHRSP were used. Three groups of SHRSP were made diabetic using streptozotocin (100 mg/kg i.p.). SHRSP from groups I (non-diabetic) and III (diabetic) chronically received L-NAME(0.5 g/L) and L-158,809 (20 mg/L) in saline to drink. Diabetic SHRSP (group C) received only saline to drink. SHRSP groups I and III developed stroke in 10+/-2 and 11+/-2 days. Average stroke-free period in groups II and IV was 18+/-2 and 29+/-2 days, respectively. Protective effect of streptozotocin-induced diabetes disappeared when SHRSP drinking L-NAME and L-158,809, also received subcutaneous injections of insulin. Present data suggest that experimental diabetes delays the onset of L-NAME-induced stroke in SHRSP and this protection is seen in the absence of renin-angiotensin system.
最近，我们已经表明，长期给予N-硝基-L-精氨酸甲酯（L-NAME，一种一氧化氮合酶抑制剂）会使易患中风的自发性高血压大鼠（SHRSP）发生中风。血管紧张素受体拮抗剂（L-158,809）被证明可延迟此类中风的发作。在本研究中，使用了五组4周龄的SHRSP。三组SHRSP用链脲佐菌素（100mg/kg腹腔注射）诱导糖尿病。来自I组（非糖尿病）和III组（糖尿病）的SHRSP长期饮用含L-NAME（0.5g/L）和L-158,809（20mg/L）的生理盐水。糖尿病SHRSP（C组）只饮用生理盐水。I组和III组的SHRSP分别在10±2天和11±2天发生中风。II组和IV组的平均无中风期分别为18±2天和29±2天。当饮用L-NAME和L-158,809的SHRSP同时接受皮下注射胰岛素时，链脲佐菌素诱导的糖尿病的保护作用消失。目前的数据表明，实验性糖尿病可延迟SHRSP中L-NAME诱导的中风发作，并且这种保护作用在肾素-血管紧张素系统缺失的情况下也可见。
