a1D-Adrenoceptors are responsible for the high sensitivity and the slow time-course of noradrenaline-mediated contraction in conductance arteries.

Autores de IIS La Fe

• Eva Serna Garcia

  Autor

• Vanessa Segura Caballer

  Autor

• Diana Vicente Miralles

  Autor

• Pilar D'ocon Navaza

  Autor

Participantes ajenos a IIS La Fe

• Flacco N
• Parés J
• Pérez-Aso M
• Noguera MA
• Ivorra MD
• McGrath JC

Abstract

The objective of this study was to determine whether the different time-course characteristics of a1-adrenoceptor-mediated contraction in arteries can be related to the subtypes involved. Contractile responses to noradrenaline (NA) were compared with inositol phosphate accumulation and extracellular signal-regulated kinase (ERK)1/2 phosphorylation after a1-agonist stimuli in the same vessels in the presence or absence of a1-antagonists in rat or in a1-subtype knockout (KO) mice. Aorta, where a1D-AR is the main functional subtype, had higher sensitivity to NA (in respect of inositol phosphate [IP], pERK1/2, and contractile response) than tail artery, where the a1A-adrenoceptor subtype is predominant. Furthermore, the contraction in aorta exhibited a slower decay after agonist removal and this was consistent in all strains harboring a1D-adrenoceptors (from rat, a1B-KO, and wild-type [WT] mice) but was not observed in the absence of the a1D-adrenoceptor signal (a1D-adrenoceptor blocked rat aorta or aorta from a1D-KO). IP formation paralleled a1-adrenoceptor-mediated contraction (agonist present or postagonist) in aorta and tail artery. High sensitivity to agonist and persistence of response after agonist removal is a property of a1D-adrenoceptors. Therefore, the preponderance of this subtype in noninnervated conductance arteries such as aorta allows responsiveness to circulating catecholamines and prevents abrupt changes in vessel caliber when the stimulus fluctuates. Conversely, in innervated distributing arteries, high local concentrations of NA are required to activate a1A-adrenoceptors for a response that is rapid but short lived allowing fine adjustment of the contractile tone by perivascular sympathetic nerves.

Keywords

• conductance and resistance vessels, contraction time-course, a1A-adrenoceptors