Nitric Oxide(NO) Primarily Accounts for Endothelium-Dependent Component of .BETA.-Adrenoceptor-Activated Smooth Muscle Relaxation of Mouse Aorta in Response to Isoprenaline.

Abstract

Isoprenaline is known to produce vascular relaxation through activation of β-adrenoceptors. In recent years, β-adrenoceptor-activated vascular relaxation has been the focus of pharmacological study in terms of both the receptor subtypes and the intracellular signaling mechanisms which trigger smooth muscle mechanical functions. In addition, the possible contribution of the endothelium to β-adrenoceptor-activated relaxation of vascular beds has provoked considerable discussion, with consensus still to be established. In the present study, we examined the effects of isoprenaline on isolated mouse aortic smooth muscles to determine whether the presence of the endothelium plays a substantial role in the relaxation it produces. A possible role for nitric oxide (NO) as a primary endothelium-derived factor released in response to isoprenaline was also elucidated pharmaco-mechanically. In isolated thoracic and abdominal aortae precontracted with phenylephrine (3 × 10 -7 -10 -6 M), isoprenaline elicited relaxation in a concentration-dependent fashion (10 -9 -10 -5 M). In endothelium-denuded preparations, isoprenaline-elicited relaxation was reduced to 40~50% of the response obtained in endothelium-intact preparations. In the preparations treated with N G -nitro-L-arginine methyl ester (L-NAME, 3 × 10 -4 M; an NO synthase inhibitor) or 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (ODQ, 10 -5 M; a soluble guanylyl cyclase inhibitor), isoprenalineelicited relaxation was attenuated almost to the same degree as the response in endothelium-denuded preparations. The degree of endothelium-dependency in isoprenaline-elicited relaxation was largely diminished when treated with propranolol (3 × 10 -6 M). The present findings indicate that isoprenaline substantially relaxes the mouse aorta with both endothelium-dependent and -independent mechanisms. The endothelium-dependent component seems to correspond to about 50% of the isoprenaline-elicited relaxation, and is almost entirely due to endothelium-derived NO. Activation of propranolol (3 × 10 -6 M)-inhibitable β-adrenoceptors seems to be primarily responsible for the NO-mediated endothelium-dependent pathway in isoprenaline-elicited Correspondence to:

Different β‐adrenoceptor subtypes coupling to cAMP or NO/cGMP pathways: implications in the relaxant response of rat conductance and resistance vessels

“…Nevertheless, there is also evidence for and against the endothelium dependence of this response due to the variability between the species and the vascular bed; inconsistency was also found even in the same vessel. Thus, Adrb-mediated relaxation has been described as being completely or partially endothelium-dependent in aorta from rat (Gray and Marshall, 1992;Brawley et al, 2000a;Ferro et al, 2004) and mouse (Akimoto et al, 2002), and as being totally endothelium-independent in rat aorta (Moncada et al, 1991;Eckly et al, 1994;Satake et al, 1996). Conflicting results have also been reported in rat MRA, where we found that Adrbmediated vasodilatation was independent of endothelial NO (Briones et al, 2005), while other authors showed NO-dependent relaxation (Graves and Poston, 1993).…”

Increased Vascular Contractility and Oxidative Stress in β₂-Adrenoceptor Knockout Mice: The Role of NADPH Oxidase

“…In this sense, acute pharmacological stimulation of β-AR induces full relaxation if the endothelial cells are intact in rat aorta [4,5] and resistance arteries [6,7,8], in mouse conductance and resistance vessels [9,10] and in human vasculature [11]. However, these results contrast with other data obtained from different species and vessel types that showed no role of the endothelium in acute relaxation mediated by β-AR agonists [12,13].…”

Effects of aging on .ALPHA.1-adrenoceptor mechanisms in the isolated mouse aortic preparation

“…However, the mouse is recently used increasingly for vascular investigation because a wide variety of gene deletion and overexpression are available in this rodent species. Accordingly, fundamental characteristics regarding vascular contraction and relaxation of normal (wild) mouse are being revealed (Akimoto et al, 2002;Ashton et al, 2000;Chan and Fiscus, 2001;Chruscinski et al, 2001;Hosoda et al, 2005;Pomerleau et al, 1997;Russell and Watts, 2000;Shibano et al, 2002;Koike, 2001a, 2001b). Distribution of α1-adrenoceptor (α1-AR) subtypes is one of such issues that are being focused.…”