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Effects Of Angiotensin-Converting Enzyme (Ace) İnhibitors And Angiotensin Receptor Blockers On Iflammatıon

Yıl 2024, Cilt: 4 Sayı: 1, 1 - 8, 22.04.2024
https://doi.org/10.58961/hmj.1463765

Öz

Background: Renin-Angiotensin system is an important system which has affected on renal, cardiovascular, inflammatory and adrenal functions. Drugs blocking this system at enzyme and receptor levels are frequently used at therapies of acute myocardial infarction, congestive heart failure, hypertension, diabetic nephropathy - proteinuria. This study aimed to reveal the effects of drugs that block this system on inflammation.
Method: In our study, the effects of three different doses of Angiotensin Converting Enzyme (ACE) inhibitors (captopril, enalapril, lisinopril) and angiotensin receptor (AT1) blocker losartan, were tested with carrageenan model on acute phase of inflammation and with cotton pellet granuloma model on chronic phase of inflammation in rats.
Results: In carrageenan model, at the second hours of the inflammation, while captopril (100 mg/kg) showed insignificant antiinflammatory effect, enalapril (20 mg/kg) and lisinopril (50 mg/kg) presented proinflammatory effects at rates of 33.35 % and 16.91 % (p<0.05). At same hour, losartan, 50 mg/kg, decreased the inflammation at rate of 43.69 %, this result was significant statistically, compared to control and diclofenac groups (p<0.05).
In the cotton pellet model, antiproliferative effects of captopril, enalapril, lisinopril, losartan, diclofenac (25 mg/kg) and prednisolone (10 mg/kg) were calculated at rates of 35.78 %,
36.87 %, 24.06 %, 30.19 %, 58.36 % and 55.11 %, respectively, and these results were significant statistically, compared to control group (p<0.05).
Conclusion: ACE inhibitors presented the proinflammatory effects in carrageenan induced acute paw oedema model, significant antiproliferative effects in chronic inflammation models. Losartan, Angiotensin receptor blocker, showed significant antiinflammatory effects in both acute and chronic inflammation models. It was thought that AT1 receptors had played important role in these effects of losartan.

Kaynakça

  • Kayaalp, S. O.: Antihipertansif İlaçlar. In: Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, 11 ed. Edited by Kayaalp, S. O.: Ankara: Hacettepe-Taş, chapt. 38, pp 372-378, 2005.
  • Yılmaz, E. D. and Kayaalp, S. O.: Peptid Yapılı Otokoidler ve Nitrik Oksid. In: Rasyonel tedavi yönünden Tıbbi Farmakoloji, 11 ed. Edi: Kayaalp, S.O.: Ankara: Hacettepe-Taş Kitapevi, chapt. 88, pp 1265-1298, 2005.
  • Sharma, J. N.: Role of tissue kallikrein-kininogen-kinin pathways in the cardiovascular system. Arch Med Res, 37: 299, 2006.
  • Dandona, P., Dhindsa, S., Ghanim, H., and Chaudhuri, A.: Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade 3. J Hum Hypertens, 21: 20, 2007.
  • Schmieder, R. E.: Mechanisms for the clinical benefits of angiotensin II receptor blockers 6. Am J Hypertens, 18: 720, 2005.
  • Bhoola, K. D., Figueroa, C. D., and Worthy, K.: Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev, 44: 1, 1992.
  • Ferreira, S. H., Moncada, S., Parsons, M., and Vane, J. R.: Proceedings: the concomitant release of bradykinin and prostaglandin in the inflammatory response to carrageenin. Br J Pharmacol, 52: 108P, 1974.
  • Agha, A. M. and Mansour, M.: Effects of captopril on interleukin-6, leukotriene B(4), and oxidative stress markers in serum and inflammatory exudate of arthritic rats: evidence of antiinflammatory activity. Toxicol Appl Pharmacol, 168: 123, 2000.
  • Ilieva, I., Ohgami, K., Jin, X. H., Suzuki, Y., Shiratori, K., Yoshida, K. et al.: Captopril suppresses inflammation in endotoxin-induced uveitis in rats. Exp Eye Res, 83: 651, 2006.
  • Miyazaki, A., Kitaichi, N., Ohgami, K., Iwata, D., Jin, X. H., Iwabuchi, K. et al.: Anti-inflammatory effect of angiotensin type 1 receptor antagonist on endotoxin- induced uveitis in rats. Graefes Arch Clin Exp Ophthalmol, 246: 747, 2008.
  • Nagai, N., Oike, Y., Noda, K., Urano, T., Kubota, Y., Ozawa, Y. et al.: Suppression of ocular inflammation in endotoxin-induced uveitis by blocking the angiotensin II type 1 receptor. Invest Ophthalmol Vis Sci, 46: 2925, 2005.
  • Zheng, Z., Chen, H., Xu, X., Li, C., and Gu, Q.: Effects of angiotensin- converting enzyme inhibitors and beta-adrenergic blockers on retinal vascular endothelial growth factor expression in rat diabetic retinopathy. Exp Eye Res, 84: 745, 2007.
  • Raghavendra, V. and Kulkarni, S. K.: AT1 receptor antagonism enhances angiotensin-II-facilitated carrageenan-induced paw edema. Methods Find Exp Clin Pharmacol, 22: 633, 2000.
  • Damas, J., Liegeois, J. F., and Simmons, W. H.: Potentiation of the pro- inflammatory effects of bradykinin by inhibition of angiotensin-converting enzyme and aminopeptidase P in rat paws. Naunyn Schmiedebergs Arch Pharmacol, 354: 670, 1996.
  • Blais, C., Jr., Leclair, P., Molinaro, G., and Adam, A.: Absence of effect of chronic angiotensin II type 1 receptor blockade on endogenous kinin concentrations- induced paw edema model in the rat. Peptides, 20: 343, 1999.
  • Boura, A. L. and Svolmanis, A. P.: Converting enzyme inhibition in the rat by captopril is accompanied by potentiation of carrageenin-induced inflammation. Br J Pharmacol, 82: 3, 1984.
  • Suda, H., Yamauchi, H., and Iso, T.: [Potentiative effects of angiotensin converting enzyme inhibitors on carrageenan-induced edema in rats]. Nippon Yakurigaku Zasshi, 80: 517, 1982.
  • Decarie, A., Adam, A., and Couture, R.: Effects of captopril and Icatibant on bradykinin (BK) and des [Arg9] BK in carrageenan-induced edema. Peptides, 17: 1009, 1996.
  • Campos, M. M., Cabrini, D. A., Cardozo, A. H., Rae, G. A., Toro, J. H., and Calixto, J. B.: Changes in paw oedema triggered via bradykinin B(1) and B(2) receptors in streptozotocin-diabetic rats. Eur J Pharmacol, 416: 169, 2001.
  • Kurihara, T., Ozawa, Y., Shinoda, K., Nagai, N., Inoue, M., Oike, Y. et al.: Neuroprotective effects of angiotensin II type 1 receptor (AT1R) blocker, telmisartan, via modulating AT1R and AT2R signaling in retinal inflammation. Invest Ophthalmol Vis Sci, 47: 5545, 2006.
  • Gepdiremen, A., Mshvildadze, V., Suleyman, H., and Elias, R.: Acute and chronic antiinflammatory effects of Hedera colchica in rats 1. J Ethnopharmacol, 94: 191, 2004.
  • Özbek, H. and Öztürk, A.: Antiinflamatuvar Etkinliğin ölçülmesinde Kullanılan Yöntemler. Van Tıp Dergisi, 10: 23, 2003.
  • Marzocco, S., Di, P. R., Serraino, I., Sorrentino, R., Meli, R., Mattaceraso, G. et al.: Effect of methylguanidine in carrageenan-induced acute inflammation in the rats. Eur J Pharmacol, 484: 341, 2004.
  • Tandon, V. R. and Gupta, R. K.: Vitex negundo Linn (VN) leaf extract as an adjuvant therapy to standard anti-inflammatory drugs. Indian J Med Res, 124: 447, 2006.

Anjiotensin Dönüştürücü Enzim İnhibitörleri Ve Angiotensin Reseptör Blokörlerinin İnflamasyona Etkisi

Yıl 2024, Cilt: 4 Sayı: 1, 1 - 8, 22.04.2024
https://doi.org/10.58961/hmj.1463765

Öz

Amaç: Renin Anjiotensin Sistemi(RAS) renal, kardiyovasküler, inflamatuvar ve adrenal fonksiyonlara etki eden önemli bir sistemdir. Bu sistemi enzim ve reseptör düzeyinde bloke eden ilaçlar, akut myokard infarktüsü, konjestif kalp yetmezliği, hipertansiyon, diyabetik nefropati-proteinüri tedavisinde yaygın olarak kullanılmaktadır. Bu çalışma, bu sistemi bloke eden ilaçların inflamasyon üzerindeki etkilerini ortaya koymayı amaçlamıştır.
Gereç ve Yöntemler: Çalışmamızda üç farklı dozda uygulanan Anjiotensin dönüştürücü enzim inhibitörleri (kaptopril, enalapril, lizinopril) ve Anjiotensin reseptör (AT1) blokeri losartan’ın inflamasyonun akut fazına etkileri karragenin inflamasyon modelinde, kronik fazına etkileri ise koton pellet granüloma modelinde sıçanlarda test edildi.
Bulgular: Karragenin modelinde, inflamasyonunun 2. saatinde kaptopril (100 mg/kg) önemsiz bir antiinflamatuvar etki yaparken, enalapril (20 mg/kg) ve lizinopril (50 mg/kg) %33.35 , ve %16.91 oranlarında proinflamatuvar etki yapmışlardır (p<0.05). Losartan(50 mg/kg) aynı saatte inflamasyonu % 43.69 oranında azaltmıştır, bu azalma kontrol ve diklofenak gruplarına oranla istatistiksel olarak anlamlı bulunmuştur (p<0.05).
Koton pellet modelinde, kaptopril, enalapril, lizinopril, losartan, diklofenak (25 mg/kg) ve prednisolon’un (10 mg/kg) antiproliferatif etkileri sırasıyla % 35.78 , % 36.87, % 24.06,
%30.19 % 58.36 ve % 55.11 olarak saptanmıştır ve bu sonuçlar kontrol grubuna oranla istatistiksel olarak anlamlıdır (p<0.05).
Sonuç: ADE inhibitörleri akut pençe ödemi modelinde proinflamatuvar, kronik inflamasyon modelinde belirgin antiproliferatif etki sergilemiştir. Losartan, hem akut hem kronik modelde önemli derecede antiinflamatuvar etki göstermiştir. Losartan’ın bu etkisinde AT1 reseptörlerin rol oynadığı düşünülmektedir.

Kaynakça

  • Kayaalp, S. O.: Antihipertansif İlaçlar. In: Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, 11 ed. Edited by Kayaalp, S. O.: Ankara: Hacettepe-Taş, chapt. 38, pp 372-378, 2005.
  • Yılmaz, E. D. and Kayaalp, S. O.: Peptid Yapılı Otokoidler ve Nitrik Oksid. In: Rasyonel tedavi yönünden Tıbbi Farmakoloji, 11 ed. Edi: Kayaalp, S.O.: Ankara: Hacettepe-Taş Kitapevi, chapt. 88, pp 1265-1298, 2005.
  • Sharma, J. N.: Role of tissue kallikrein-kininogen-kinin pathways in the cardiovascular system. Arch Med Res, 37: 299, 2006.
  • Dandona, P., Dhindsa, S., Ghanim, H., and Chaudhuri, A.: Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade 3. J Hum Hypertens, 21: 20, 2007.
  • Schmieder, R. E.: Mechanisms for the clinical benefits of angiotensin II receptor blockers 6. Am J Hypertens, 18: 720, 2005.
  • Bhoola, K. D., Figueroa, C. D., and Worthy, K.: Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev, 44: 1, 1992.
  • Ferreira, S. H., Moncada, S., Parsons, M., and Vane, J. R.: Proceedings: the concomitant release of bradykinin and prostaglandin in the inflammatory response to carrageenin. Br J Pharmacol, 52: 108P, 1974.
  • Agha, A. M. and Mansour, M.: Effects of captopril on interleukin-6, leukotriene B(4), and oxidative stress markers in serum and inflammatory exudate of arthritic rats: evidence of antiinflammatory activity. Toxicol Appl Pharmacol, 168: 123, 2000.
  • Ilieva, I., Ohgami, K., Jin, X. H., Suzuki, Y., Shiratori, K., Yoshida, K. et al.: Captopril suppresses inflammation in endotoxin-induced uveitis in rats. Exp Eye Res, 83: 651, 2006.
  • Miyazaki, A., Kitaichi, N., Ohgami, K., Iwata, D., Jin, X. H., Iwabuchi, K. et al.: Anti-inflammatory effect of angiotensin type 1 receptor antagonist on endotoxin- induced uveitis in rats. Graefes Arch Clin Exp Ophthalmol, 246: 747, 2008.
  • Nagai, N., Oike, Y., Noda, K., Urano, T., Kubota, Y., Ozawa, Y. et al.: Suppression of ocular inflammation in endotoxin-induced uveitis by blocking the angiotensin II type 1 receptor. Invest Ophthalmol Vis Sci, 46: 2925, 2005.
  • Zheng, Z., Chen, H., Xu, X., Li, C., and Gu, Q.: Effects of angiotensin- converting enzyme inhibitors and beta-adrenergic blockers on retinal vascular endothelial growth factor expression in rat diabetic retinopathy. Exp Eye Res, 84: 745, 2007.
  • Raghavendra, V. and Kulkarni, S. K.: AT1 receptor antagonism enhances angiotensin-II-facilitated carrageenan-induced paw edema. Methods Find Exp Clin Pharmacol, 22: 633, 2000.
  • Damas, J., Liegeois, J. F., and Simmons, W. H.: Potentiation of the pro- inflammatory effects of bradykinin by inhibition of angiotensin-converting enzyme and aminopeptidase P in rat paws. Naunyn Schmiedebergs Arch Pharmacol, 354: 670, 1996.
  • Blais, C., Jr., Leclair, P., Molinaro, G., and Adam, A.: Absence of effect of chronic angiotensin II type 1 receptor blockade on endogenous kinin concentrations- induced paw edema model in the rat. Peptides, 20: 343, 1999.
  • Boura, A. L. and Svolmanis, A. P.: Converting enzyme inhibition in the rat by captopril is accompanied by potentiation of carrageenin-induced inflammation. Br J Pharmacol, 82: 3, 1984.
  • Suda, H., Yamauchi, H., and Iso, T.: [Potentiative effects of angiotensin converting enzyme inhibitors on carrageenan-induced edema in rats]. Nippon Yakurigaku Zasshi, 80: 517, 1982.
  • Decarie, A., Adam, A., and Couture, R.: Effects of captopril and Icatibant on bradykinin (BK) and des [Arg9] BK in carrageenan-induced edema. Peptides, 17: 1009, 1996.
  • Campos, M. M., Cabrini, D. A., Cardozo, A. H., Rae, G. A., Toro, J. H., and Calixto, J. B.: Changes in paw oedema triggered via bradykinin B(1) and B(2) receptors in streptozotocin-diabetic rats. Eur J Pharmacol, 416: 169, 2001.
  • Kurihara, T., Ozawa, Y., Shinoda, K., Nagai, N., Inoue, M., Oike, Y. et al.: Neuroprotective effects of angiotensin II type 1 receptor (AT1R) blocker, telmisartan, via modulating AT1R and AT2R signaling in retinal inflammation. Invest Ophthalmol Vis Sci, 47: 5545, 2006.
  • Gepdiremen, A., Mshvildadze, V., Suleyman, H., and Elias, R.: Acute and chronic antiinflammatory effects of Hedera colchica in rats 1. J Ethnopharmacol, 94: 191, 2004.
  • Özbek, H. and Öztürk, A.: Antiinflamatuvar Etkinliğin ölçülmesinde Kullanılan Yöntemler. Van Tıp Dergisi, 10: 23, 2003.
  • Marzocco, S., Di, P. R., Serraino, I., Sorrentino, R., Meli, R., Mattaceraso, G. et al.: Effect of methylguanidine in carrageenan-induced acute inflammation in the rats. Eur J Pharmacol, 484: 341, 2004.
  • Tandon, V. R. and Gupta, R. K.: Vitex negundo Linn (VN) leaf extract as an adjuvant therapy to standard anti-inflammatory drugs. Indian J Med Res, 124: 447, 2006.
Toplam 24 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Klinik Tıp Bilimleri (Diğer)
Bölüm Araştırma Makaleleri
Yazarlar

Fulden Küçük 0000-0002-7929-3453

Günnur Özbakış Dengiz 0000-0003-1117-3575

Zekiye Nur Banoğlu 0000-0002-2584-5822

Yayımlanma Tarihi 22 Nisan 2024
Gönderilme Tarihi 2 Nisan 2024
Kabul Tarihi 17 Nisan 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 4 Sayı: 1

Kaynak Göster

Vancouver Küçük F, Özbakış Dengiz G, Banoğlu ZN. Anjiotensin Dönüştürücü Enzim İnhibitörleri Ve Angiotensin Reseptör Blokörlerinin İnflamasyona Etkisi. HTD / HMJ. 2024;4(1):1-8.

e-ISSN: 2791-9935