Kaptopril, enalapril ve silazapril' in endotel-kaynaklı nitrik oksid ile ilişkisinin in vitro olarak karşılaştırlması

Son yıllarda angiotensin konverting enzim (ACE) inhibitörlerinin nitrik oksit (NO) ile ilişkili olarak aterosklerozdan koruyucu etkileri olduğu bildirilmiştir. Bu amaçla ülkemizde bulunan kaptopril (K), enalapril (E), silazapril (S)'in normotensif annelerin sağlıklı bebeklerinin umbilikal arter segmentleri kullanılarak NO ile ilişkisi araştırıldı. Önceden 10-1 M konsantrasyonda BaCl2 ile kasılan umbilikal arter şeritlerinin 10-8'den 10-4 M konsantrasyonlarda K, E ve S ile tek başına ve bir guanilat siklaz inhibitörü olan metilen mavisi (MV) eklenerek maksimum gevşeme cevapları ölçüldü. K ile maksimum gevşeme cevabı 10-7, 10-6, 10-5, 10-4 konsantrasyonlarında MV eklenerek elde edilenlerden anlamlı şekilde daha fazlaydı (p

Comparison of captopril, enalapril's relation with endothelium-derived nitric oxide as in vitro

Recently, it was reported that atherosclerosis is associated with vascular endothelial dysfunction and reduced nitric oxide (NO) activity. Enhancement of NO activity may have an antiatherogenic action. This study was performed to investigate the role of NO on the vasodilatory effect of captopril (K), enalapril (E), cilazapril (S) on isolated human umbilical artery strips. Umbilical artery strips were precontracted by 10-1 M BaCl2 and then angiotensin converting enzyme inhibitors (ACEIs) alone were added in 10-8 to 10-4 M concentrations, and relaxation responses for ACEIs were measured. The same investigations and measurements were repeated after incubation of artery strips with methylene blue (MV) for 30 minutes. Maximum relaxation responses with K were stronger at consentrations of 10-7, 10-6, 10-4 than those of incubated with MV (p<0.05). Maximum relaxation responses with E were stronger at consentrations of 10-6, 10-5, 10-4 than those of incubated with MV (p<0.05). Similarly, Maximum relaxation responses with S were stronger at consentrations of 10-5, 10-4 than those of incubated with MeB (p<0.05). K's mazimum relaxation responses were more stronger than those of other ACEIs (p<0.05). We think that the sulfhydryl-containing ACEIs, such as captopril, have stronger relaxation effect compared to other ones. To determine effects of ACEI on atherosclerosis development, comperative studies should be done.

Kaynakça

1- Ruschitzka F, Noll G, Luscher TF: Angiotensin converting enzyme inhibitors and vascular protection in hypertension. J Cardiovasc Pharmacol 34: 3-12, 1999.

2- Persson K, Andersson RG: Nitric oxide modulates captopril-mediated angiotensin-converting enzyme inhibition in porcine iliac arteries. Eur J Pharmacol 385: 21-7, 1999.

3- Weber MA: Interrupting the renin-angiotensin system: the role of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the treatment of hypertension. Am J Hypertens 12:189-194, 1999.

4- Prasad A, Husain S, Quyyumi AA: Effect of enalaprilat on nitric oxide activity in coronary artery disease. Am J Cardiol 84:1-6, 1999.

5- Channon KM, Qian H, George SE: Nitric oxide synthase in atherosclerosis and vascular injury: insights from experimental gene therapy. Arterioscler Thromb Vasc Biol 20:1873-81, 2000.

6- Taddei S, Virdis A, Ghiadoni L, Salvetti G, Salvetti A: Endothelial dysfunction in hypertension. J Nephrol 13: 205-10, 2000

7- Kitagawa S, Yamaguchi Y, Kunitomo M, Sameshima E, Fujiwara M: NG-nitro-L-arginine-resistant endothelium-dependent relaxation induced by acetylcholine in the rabbit renal artery. Life Sci 55: 491-8, 1994.

8- Duarte J, Martinez A, Bermejo A, Vera B, Gamez MJ, Cabo P, Zarzuelo A: Cardiovascular effects of captopril and enalapril in obese Zucker rats. Eur J Pharmacol 365: 225-32, 1999.

9- Haklar G, Ersahin C, Moini H, Sungun M, Dogan N, Bilsel S, Emerk K, Yalcin AS: Protective effects of cilazapril against free radical injury in myocardial ischaemia-reperfusion. Pharmacol Res 31: 33-6, 1999.

10- Anning PB, Grocott-Mason RM, Lewis MJ: Effects of sulphydryl- and non-sulphydryl-containing ACE inhibitors on left ventricular relaxation in the isolated guinea pig heart. Endothelium 5: 265-75, 1997.

Kaynak Göster