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Application of a Chymase Inhibitor, NK3201, for Prevention of Vascular Proliferation
| Content Provider | Scilit |
|---|---|
| Author | Takai, Shinji Miyazaki, Mizuo |
| Copyright Year | 2006 |
| Description | Journal: Cardiovascular drug reviews NK3201 is an orally active chymase inhibitor. Its inhibitory activity leads to formation of acyl‐intermediate between active serine residue of the enzyme and di‐ketone structure of NK3201. NK3201 inhibits human, dog and hamster chymases with $IC_{50}$ of 2.5, 1.2, and 28 nM, respectively. On the other hand, NK3201 does not inhibit other types of serine proteases, tryptase, thrombin, elastase, plasmin, and plasminogen activator. In dogs, at 8 h after oral administration of NK3201, 1 mg/kg, the drug levels in plasma, heart, and aorta reached 470, 195, and 78 nM, respectively. In a dog model NK3201, 5 mg/kg/day, increased chymase activity in grafted veins, and suppressed vascular proliferation. After balloon injury in dog vessels, chymase activity was increased locally, in the injured artery, and NK3201, 1 mg/kg/day was effective in preventing vascular proliferation. On the other hand, NK3201, unlike angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, did not affect blood pressure. These findings indicate that local angiotensin II production by chymase is involved only in vascular proliferation, as seen in the injured vessels. Therefore, NK3201 may be useful for preventing vascular proliferation without affecting blood pressure. |
| Related Links | https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1527-3466.2003.tb00115.x |
| Ending Page | 198 |
| Page Count | 14 |
| Starting Page | 185 |
| ISSN | 08975957 |
| e-ISSN | 15273466 |
| DOI | 10.1111/j.1527-3466.2003.tb00115.x |
| Journal | Cardiovascular drug reviews |
| Issue Number | 3 |
| Volume Number | 21 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2006-06-07 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cardiovascular drug reviews Peripheral Vascular Disease Vascular Proliferation Chymase Inhibitors |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Cardiology and Cardiovascular Medicine |
