α(1D)-Adrenoceptors are responsible for the high sensitivity and the slow time-course of noradrenaline-mediated contraction in conductance arteries

The objective of this study was to determine whether the different time-course characteristics of α(1)-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 α(1)-agonist stimuli in the same vessels in the presence or absence of α(1)-antagonists in rat or in α(1)-subtype knockout (KO) mice. Aorta, where α(1D)-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 α(1A)-adrenoceptor subtype is predominant. Furthermore, the contraction in aorta exhibited a slower decay after agonist removal and this was consistent in all strains harboring α(1D)-adrenoceptors (from rat, α(1B)-KO, and wild-type [WT] mice) but was not observed in the absence of the α(1D)-adrenoceptor signal (α(1D)-adrenoceptor blocked rat aorta or aorta from α(1D)-KO). IP formation paralleled α(1)-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 α(1D)-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 α(1A)-adrenoceptors for a response that is rapid but short lived allowing fine adjustment of the contractile tone by perivascular sympathetic nerves.