Functional characterization of α₁‐adrenoceptor subtypes in vascular tissues using different experimental approaches:a comparative study

Abstract

1 The a 1 -adrenergic responses of rat aorta and tail artery have been analysed measuring the contractility and the inositol phosphate (IP) formation induced by noradrenaline. Three antagonists, prazosin, 5-methylurapidil (a 1A selective) and BMY 7378 (a 1D selective) have been used in di erent experimental procedures. 2 Noradrenaline possesses a greater potency inducing contraction and IP accumulation in aorta (pEC 50 -contraction=7.32+0.04; pEC 50 -IPs=6.03+0.08) than in the tail artery (pEC 50 -contraction=5.71+0.07; pEC 50 -IPs=5.51+0.10). Although the maximum contraction was similar in both tissues (E max -tail=619.1+55.6 mg; E max -aorta-698.2+40.8 mg), there were marked di erences in the ability of these tissues to generate intracellular second messengers the tail artery being more e cient (E max -tail=1060+147%; E max -aorta=108.1+16.9%).3 Concentration response curves of noradrenaline in presence of antagonist together with concentration inhibition curves for antagonists added before (CICb) or after (CICa) noradrenaline-induced maximal response in Ca 2+ -containing or Ca 2+ -free medium have been performed. A comparative analysis of the di erent procedures as well as the mathematical approaches used in each case to calculate the antagonist potencies, were completed. 4 The CICa was the simplest method to characterize the predominant a 1 -adrenoceptor subtype involved in the functional response of a tissue. 5 In aorta, where constitutively active a 1D -adrenoeptors are present, the use of di erent experimental procedures evidenced a complex equilibrium between a 1D -and a 1A -adrenoceptor subtypes. 6 The appropriate management of LiCl in IP accumulation studies allowed us to reproduce the di erent experimental procedures performed in contractile experiments giving more technical possibilities to this methodology.

Orthostatic hypotensive effect of antipsychotic drugs in Wistar rats by in vivo and in vitro studies of α1-adrenoceptor function

“…A major functional role of α 1A in MSA has also been proposed by other authors (Ipsen et al 1997;Stam et al 1999), whereas several lines of evidence show that the α 1D -subtype is the main functional α 1 -AR subtype in rat aorta (Hussain and Marshall 1997;Hrometz et al 1999;Gisbert et al 2003). Although there are some functional studies on spleen and liver indicating the presence of α 1B -AR in these tissues (Sleight et al 1993;Eltze 1996), as yet there is little direct evidence for the role of the α 1B -AR as a mediator of contractile function in blood vessels (Daly et al 2002).…”

The Impact of α1-Adrenoceptors Up-Regulation Accompanied by the Impairment of β-Adrenergic Vasodilatation in Hypertension

“…An average of six readings was recorded for each animal. Thoracic aortas were obtained as described previously (Gisbert et al, 2003a). This research work conforms with the Guide for Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, 1996) and was also approved by the Ethics Committee of the University of Valencia (Valencia, Spain).…”

Alpha‐1D adrenoceptors are involved in reserpine‐induced supersensitivity of rat tail artery

“…These subtypes distribute distinctly and play key roles in adrenergic functions in many tissues (McGrath & Wilson, 1988;Muramatsu et al, 1995;Graham et al, 1996;Daly et al, 2002). In rats, for example, the adrenergic contraction of the tail artery is predominantly mediated by the alpha-1A AR subtype (Lachnit et al, 1997;Murata et al, 1999;Gisbert et al, 2003), while the adrenergic contractions of the thoracic aorta and spleen are mainly through alpha-1D and alpha-1B AR subtypes, respectively (Burt et al, 1995;Muramatsu et al, 1995;Buckner et al, 1996;Saussy et al, 1996). Recent studies further developed various drugs specific for each subtype.…”