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α 1 ‐Adrenoceptor vasoconstriction in the tail artery during ageing
Author(s) -
Vila Elisabet,
Vivas Nuria M,
Tabernero Antonia,
Giraldo Jesús,
Arribas Silvia M
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701193
Subject(s) - phenoxybenzamine , medicine , endocrinology , vasoconstriction , prazosin , chemistry , receptor , contraction (grammar) , endothelium , vasodilation , biology , antagonist
We have studied the α 1 ‐adrenoceptor‐mediated responses in intact tail artery rings from 3–4 and 20–22 months old Sprague‐Dawley rats, focusing on possible endothelial alterations. The influence of nitric oxide released by the endothelium, the number of α 1 ‐adrenoceptors and the functional receptor reserve were evaluated to determine their contribution to the contractile response mediated by this receptor. The state of the endothelial layer was assessed by confocal microscopy. Noradrenaline (1 n M –100 μ M ) induced concentration‐dependent vasoconstriction. The maximum contractions to noradrenaline ( P <0.05) and to 75 m M KCl ( P <0.01) were higher in young than in old animals. The density (B max ) of α 1 ‐adrenoceptors and the dissociation constant ( K D ) obtained in [ 3 H]‐prazosin binding experiments were unchanged by age. The apparent affinity (p K A ) and the percentage of functional receptors (qx100) remaining after phenoxybenzamine (0.03 μ M ) were similar in both age groups. After partial α 1 ‐adrenoceptor inactivation with phenoxybenzamine, N G ‐nitro‐ L ‐arginine methylester (30 μ M ) significantly potentiated the E/[A] curve to noradrenaline in young rats. However, only responses to 0.1 to 1 μ M noradrenaline were significantly potentiated in old animals. In addition, 94% of the vessels from young, but only 52% from old rats were relaxed by 80–100% of the noradrenaline (0.03 μ M ) contraction, with 1 μ M acetylcholine. No modifications in the area (μm 2 ) or in the number of endothelial nuclei (per mm 2 ) were observed between age groups. An elongation of the nuclei of endothelial cells was observed in the old animals. These data suggest that the noradrenaline‐induced contraction is decreased in old rats probably due to differences in either the contractile machinery or postreceptor mechanisms. These alterations may be accompanied by an impairment of the release or production of NO from endothelial cells.