Araştırma Makalesi
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Beta adrenergic receptors play role in the vasoconstrictor effect of dobutamine in the isolated rat aorta

Yıl 2020, , 613 - 619, 18.09.2020
https://doi.org/10.31362/patd.700611

Öz

Purpose: Experimental evidence exists that cardiac action of dobutamine is mediated by alfa-1 and beta- adrenergic receptors. However, uncertainty remains regarding the vascular effect of dobutamine and contribution of beta-adrenergic receptors to this effect. The aim of the present study was to investigate the direct effect of dobutamine in the rat aorta and the role of beta-adrenergic receptors in this effect.
Materials and methods: The isolated thoracic aortic rings were mounted in organ bath containing Krebs-Henseleit solution. After an equilibiration period, endothelial integrity was then checked by the response to acetylcholine (10 μM) in aortic rings pre-contracted with phenylephrine (1 μM). After washout, dobutamine (0.001-10 μM) was added to generate cumulative concentration–response curves (CCRCs). To investigate the role of alfa- and beta- adrenergic receptors in the dobutamine-induced vascular response, prazosin (0.0003 µM) or propranolol (1 µM) was added to the bath medium 30 min before the addition of dobutamine in some experiments..
Results: Dobutamine produced concentration-dependent contraction in the endothelium-intact isolated rat aorta. This effect was significantly inhibited by either propranolol or prazosin (p<0.05). Prazosin also significantly supressed the maximum vascular response obtained by dobutamine (p<0.05).
Conclusion: The results, to the best of my knowledge, demonstrates for the first time that beta-adrenergic receptors are involved in the vasoconstrictor effect of dobutamine in the endothelium-intact rat aorta.

Teşekkür

I would like to thank to Zeynep Elif YEŞİLYURT (PhD student at Ankara University Faculty of Pharmacy Department of Pharmacology) for technical support.

Kaynakça

  • References 1. Tuttle RR, Mills J.Dobutamine: development of new catecholamine to selectively increase cardiac contractility. Circ Res. 1975; 36(1): 185–96. 2. Kenakin TP. An in vitro quantitative analysis of the alpha adrenoceptor partial agonist activity of dobutamine and its relevance to inotropic selectivity. J Pharmacol Exp Ther 1981; 216 (2): 210–219. 3. Kenakin TP, Johnson SF. The importance of the alpha-adrenoceptor agonist activity of dobutamine to inotropic selectivity in the anaesthetized cat. Eur J Pharmacol. 1985; 111(3):347–54. 4. Ruffolo RRJr, Spradlin TA, Pollock GD, Waddell JE, Murphy PJ. Alpha and beta adrenergic effects of the stereoisomers of dobutamine. J Pharmacol Exp Ther 1981; 219 (2): 447–452. 5. Oriowo MA, Nichols AJ, Ruffolo RR Jr. Receptor protection studies with phenoxybenzamine indicate that a single alpha 1-adrenoceptor may be coupled to two signal transduction processes in vascular smooth muscle.Pharmacology 1992; 45(1): 17–26. 6. Oriowo MA. Alpha1-adrenoceptor antagonist effect of (+/-)-dobutamine in rat isolated gastric artery preparation. J Cardiovasc Pharmacol. 1999; 34(5):728–33. 7. Flacco N, Segura V, Perez-Aso M, et al. Different β adrenoceptor subtypes coupling to cAMP or NO/cGMP pathways: implications in the relaxant response of rat conductance and resistance vessels. Br J Pharmacol. 2013;169(2):413–425. 8. Pourageaud F, Leblais V, Bellance N, Marthan R, Muller B. Role of beta2-adrenoceptors (beta-AR), but not beta1-, beta3-AR and endothelial nitric oxide, in beta-AR-mediated relaxation of rat intrapulmonary artery. Naunyn Schmiedebergs Arch Pharmacol. 2005; 372(1):14–23. 9. Randall MD, McCulloch AI. The involvement of ATP-sensitive potassium channels in beta-adrenoceptor-mediated vasorelaxation in the rat isolated mesenteric arterial bed. Br J Pharmacol. 1995;115(4):607–612. 10. Waldeck B. "The β1-selective adrenoceptor agonist dobutamine": a fallacy being perpetuated. Chirality. 2011; 23(1):63–64. 11. Ruffolo RR Jr, Yaden EL. Vascular effects of the stereoisomers of dobutamine. J Pharmacol Exp Ther. 1983; 224(1): 46–50. 12. Kenakin TP.An in vitro quantitative analysis of the alpha adrenoceptor partial agonist activity of dobutamine and its relevance to inotropic selectivity, J Pharmacol ExpTher 1981; 216 (2): 210–219. 13. Kenakin, TP. Organ selectivity of drugs. Alternatives to receptor selectivity, Trends Pharmacol Sci 1982; 4:153. 14. Baker JG. The selectivity of beta-adrenoceptor agonists at human beta1-, beta2- and beta3-adrenoceptors. Br J Pharmacol. 2010;160(5):1048-61. 15. Werstiuk ES, Lee RM. Vascular beta-adrenoceptor function in hypertension and in ageing. Can J Physiol Pharmacol. 2000 Jun;78(6):433-52. 16. Félétou M, Vanhoutte PM. Endothelial dysfunction: a multifaceted disorder. Am J Physiol Heart Circ Physiol. 2006; 91(3): H985-1002. 17. Pourageaud F, Leblais V, Bellance N, Marthan R, Muller B. Role of beta2-adrenoceptors (beta-AR), but not beta1-, beta3-AR and endothelial nitric oxide, in beta-AR-mediated relaxation of rat intrapulmonary artery. Naunyn Schmiedebergs Arch Pharmacol. 2005; 372(1):14-23. 18. Mori A, Miwa T, Sakamoto K, et al. Pharmacological evidence for the presence of functional beta(3)-adrenoceptors in rat retinal blood vessels. Naunyn Schmiedebergs Arch Pharmacol. 2010; 382:119-26. 19. Mahajan P, Tabrizchi R. Influence of endothelium on beta-adrenoceptor-mediated mechanical and electrical functions in rat pulmonary artery. Vascul Pharmacol. 2010; 53(3-4):144-50.

İzole sıçan aortunda dobutaminin vazokonstriktör etkisinde beta adrenerjik reseptörler rol oynar

Yıl 2020, , 613 - 619, 18.09.2020
https://doi.org/10.31362/patd.700611

Öz

Amaç: Alfa-1 ve beta-adrenerjik reseptörlerin, dobutaminin kardiyak etkisine aracılık ettiğine ilişkin deneysel kanıt mevcuttur. Ancak, dobutaminin vasküler etkisi ve bu etkiye beta-adrenerjik reseptörlerin katkısı belirsizliğini korumaktadır. Bu çalışma, dobutaminin sıçan aortundaki doğrudan etkisini ve bu etkide beta adrenerjik reseptörlerin rolünü araştırmayı amaçlamıştır.
Gereç ve yöntem: İzole edilmiş torasik aort halkaları Krebs-Henseleit solüsyonu içeren organ banyosuna asıldı. Dinlenme periyodu sonrası, aort halkaları fenilefrinle (1 μM) kasıldıktan sonra verilen asetilkolin (10 μM) yanıtıyla endotelyal bütünlük kontrol edildi. Yıkama sonrası, dobutamin (0.001-10 μM), kümülatif konsantrasyon-yanıt eğrilerini elde etmek için organ banyosuna eklendi. Dobutaminin oluşturduğu vasküler yanıtta alfa- ve beta-adrenerjik reseptörlerin rolünü araştırmak için, bazı deneylerde, prazosin (0.0003 µM) veya propranolol (1 µM) banyo ortamına dobutaminden 30 dakika önce eklendi.
Bulgular: Dobutamin, endoteli sağlam izole sıçan aortunda konsantrasyon-bağımlı kontraksiyona neden oldu. Bu etki, propranolol veya prazosin varlığında anlamlı olarak inhibe edildi (p<0.05). Ayrıca, prazosin dobutaminle elde edilen maksimum vasküler yanıtı da baskıladı (p<0.05).
Sonuç: Bu sonuçlar, bildiğim kadarıyla, ilk defa endoteli sağlam izole sıçan aortunda dobutaminin vazokonstriktör etkisinde beta-adrenerjik reseptörlerin ilişkisi olduğunu göstermektedir.

Kaynakça

  • References 1. Tuttle RR, Mills J.Dobutamine: development of new catecholamine to selectively increase cardiac contractility. Circ Res. 1975; 36(1): 185–96. 2. Kenakin TP. An in vitro quantitative analysis of the alpha adrenoceptor partial agonist activity of dobutamine and its relevance to inotropic selectivity. J Pharmacol Exp Ther 1981; 216 (2): 210–219. 3. Kenakin TP, Johnson SF. The importance of the alpha-adrenoceptor agonist activity of dobutamine to inotropic selectivity in the anaesthetized cat. Eur J Pharmacol. 1985; 111(3):347–54. 4. Ruffolo RRJr, Spradlin TA, Pollock GD, Waddell JE, Murphy PJ. Alpha and beta adrenergic effects of the stereoisomers of dobutamine. J Pharmacol Exp Ther 1981; 219 (2): 447–452. 5. Oriowo MA, Nichols AJ, Ruffolo RR Jr. Receptor protection studies with phenoxybenzamine indicate that a single alpha 1-adrenoceptor may be coupled to two signal transduction processes in vascular smooth muscle.Pharmacology 1992; 45(1): 17–26. 6. Oriowo MA. Alpha1-adrenoceptor antagonist effect of (+/-)-dobutamine in rat isolated gastric artery preparation. J Cardiovasc Pharmacol. 1999; 34(5):728–33. 7. Flacco N, Segura V, Perez-Aso M, et al. Different β adrenoceptor subtypes coupling to cAMP or NO/cGMP pathways: implications in the relaxant response of rat conductance and resistance vessels. Br J Pharmacol. 2013;169(2):413–425. 8. Pourageaud F, Leblais V, Bellance N, Marthan R, Muller B. Role of beta2-adrenoceptors (beta-AR), but not beta1-, beta3-AR and endothelial nitric oxide, in beta-AR-mediated relaxation of rat intrapulmonary artery. Naunyn Schmiedebergs Arch Pharmacol. 2005; 372(1):14–23. 9. Randall MD, McCulloch AI. The involvement of ATP-sensitive potassium channels in beta-adrenoceptor-mediated vasorelaxation in the rat isolated mesenteric arterial bed. Br J Pharmacol. 1995;115(4):607–612. 10. Waldeck B. "The β1-selective adrenoceptor agonist dobutamine": a fallacy being perpetuated. Chirality. 2011; 23(1):63–64. 11. Ruffolo RR Jr, Yaden EL. Vascular effects of the stereoisomers of dobutamine. J Pharmacol Exp Ther. 1983; 224(1): 46–50. 12. Kenakin TP.An in vitro quantitative analysis of the alpha adrenoceptor partial agonist activity of dobutamine and its relevance to inotropic selectivity, J Pharmacol ExpTher 1981; 216 (2): 210–219. 13. Kenakin, TP. Organ selectivity of drugs. Alternatives to receptor selectivity, Trends Pharmacol Sci 1982; 4:153. 14. Baker JG. The selectivity of beta-adrenoceptor agonists at human beta1-, beta2- and beta3-adrenoceptors. Br J Pharmacol. 2010;160(5):1048-61. 15. Werstiuk ES, Lee RM. Vascular beta-adrenoceptor function in hypertension and in ageing. Can J Physiol Pharmacol. 2000 Jun;78(6):433-52. 16. Félétou M, Vanhoutte PM. Endothelial dysfunction: a multifaceted disorder. Am J Physiol Heart Circ Physiol. 2006; 91(3): H985-1002. 17. Pourageaud F, Leblais V, Bellance N, Marthan R, Muller B. Role of beta2-adrenoceptors (beta-AR), but not beta1-, beta3-AR and endothelial nitric oxide, in beta-AR-mediated relaxation of rat intrapulmonary artery. Naunyn Schmiedebergs Arch Pharmacol. 2005; 372(1):14-23. 18. Mori A, Miwa T, Sakamoto K, et al. Pharmacological evidence for the presence of functional beta(3)-adrenoceptors in rat retinal blood vessels. Naunyn Schmiedebergs Arch Pharmacol. 2010; 382:119-26. 19. Mahajan P, Tabrizchi R. Influence of endothelium on beta-adrenoceptor-mediated mechanical and electrical functions in rat pulmonary artery. Vascul Pharmacol. 2010; 53(3-4):144-50.
Toplam 1 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İç Hastalıkları
Bölüm Araştırma Makalesi
Yazarlar

Hande Ozge Altunkaynak-camca 0000-0002-4547-7756

Yayımlanma Tarihi 18 Eylül 2020
Gönderilme Tarihi 9 Mart 2020
Kabul Tarihi 17 Haziran 2020
Yayımlandığı Sayı Yıl 2020

Kaynak Göster

AMA Altunkaynak-camca HO. Beta adrenergic receptors play role in the vasoconstrictor effect of dobutamine in the isolated rat aorta. Pam Tıp Derg. Eylül 2020;13(3):613-619. doi:10.31362/patd.700611
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