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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Nakajima, S. Hayashi, I. Izumi, T. Ito, H. Majima, M. Katori, M. |
| Description | Author Affiliation: Ito H ( Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.) |
| Abstract | The effect of prolonged administration of a carboxypeptidase Y-like kininase inhibitor, ebelactone B (EB) (2-ethyl-3, 11-dihydroxy-4, 6, 8, 10, 12-pentamethyl-9-oxo-6-tetradecenoic 1, 3-lactone), on the development of deoxycorticosterone acetate (DOCA)-salt hypertension was tested. The systolic blood pressure (SBP) of non-treated 6-week-old Sprague-Dawley strain rats was gradually increased by DOCA-salt treatment from 137+/-2 mmHg (n=11) to 195+/-7 mmHg at 10 weeks of age. With daily oral administration of lisinopril (5 mg kg(-1), twice a day), which is an inhibitor of angiotensin converting enzyme, a major kininase in plasma, the development of hypertension was not suppressed. By contrast, administration of EB (5 mg kg(-1), twice a day), completely inhibited the development of hypertension (SBP: 146+/-1 mmHg, n=5, 10 weeks old). The reduced SBP at 10 weeks of age was equal to the SBP before any treatment (142+/-1 mmHg, n=5). Direct determination of mean blood pressure (MBP) in conscious, unrestrained rats confirmed that MBP elevation was completely inhibited by EB. Continuous subcutaneous infusion (5 mg kg(-1) day(-1)) of HOE140, a bradykinin B2 receptor antagonist, restored the elevation of SBP, which was suppressed by EB. The weights of left ventricle of DOCA-salt treated rats 10-weeks-old (0.36+/-0.02 g 100 g body weight(-1), n=11) was significantly reduced by EB (0.27+/-0.01, n=5), as were the sodium levels in serum, cerebrospinal fluid and erythrocyte. These findings suggested that EB is effective in preventing salt-related hypertension presumably by eliminating sodium retention. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 126 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-02-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Antihypertensive Agents Pharmacology Carboxypeptidases Antagonists & Inhibitors Hypertension Prevention & Control Angiotensin-Converting Enzyme Inhibitors Animals Therapeutic Use Blood Pressure Drug Effects Bradykinin Analogs & Derivatives Bradykinin Receptor Antagonists Urine Cathepsin A Desoxycorticosterone Heart Growth & Development Heart Ventricles Chemically Induced Kallikreins Kidney Kinins Lactones Lisinopril Organ Size Protease Inhibitors Rats, Sprague-Dawley Specific Pathogen-Free Organisms Thiorphan Time Factors Urination Water-Electrolyte Balance |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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