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

Year 2020, , 613 - 619, 18.09.2020

Hande Ozge Altunkaynak-camca

https://doi.org/10.31362/patd.700611

Abstract

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.

Keywords

Dobutamine, alfa adrenergic receptor, beta adrenergic receptor, vasoconstriction

Thanks

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

İzole sıçan aortunda dobutaminin vazokonstriktör etkisinde beta adrenerjik reseptörler rol oynar

Abstract

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.

Keywords

Dobutamin, alfa adrenerjik reseptör, beta adrenerjik reseptör, vazokonstriksiyon

References

• 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.