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α<inf>1</inf>-adrenoceptor vasoconstriction in the tail artery during ageing

Abstract:

1. We have studied the α1-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 α1-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. 2. Noradrenaline (1 nM-100 nM) induced concentration-dependent vasoconstriction. The maximum contractions to noradrenaline (P < 0.05) and to 75 mM KCl (P < 0.01) were higher in young than in old animals. 3. The density (B(max)) of α1-adrenoceptors and the dissociation constant (K(D)) obtained in [3H]-prazosin binding experiments were unchanged by age. 4. The apparent affinity (pK(A)) and the percentage of functional receptors (q x 100) remaining after phenoxybenzamine (0.03 μM) were similar in both age groups. 5. After partial a-adrenoceptor inactivation with phenoxybenzamine, N(G)-nitro-L-arginine methylester (30 μM) significantly potentiated the E/[A] curve to noradrenaline in young rats. However, only responses to 0.1 to 1 μM 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 μM) contraction, with 1 nM acetylcholine. 6. No modifications in the area (μm2) or in the number of endothelial nuclei (per mm2) were observed between age groups. An elongation of the nuclei of endothelial cells was observed in the old animals. 7. 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.