ALPHA(1)-ADRENOCEPTOR VASOCONSTRICTION IN THE TAIL ARTERY DURING AGING

1 We have studied the alpha(1)-adrenoceptor-mediated responses in inta ct tail artery rings from 3-4 and 20-22 months old Sprague-Dawley rats , focusing on possible endothelial alterations. The influence of nitri c oxide released by the endothelium, the number of alpha(1)-adrenocept ors and the functional receptor reserve were evaluated to determine th eir contribution to the contractile response mediated by this receptor . The state of the endothelial layer was assessed by confocal microsco py. 2 Noradrenaline (1 nM - 100 mu M) induced concentration-dependent vasoconstriction. The maximum contractions to noradrenaline (P < 0.05) and to 75 mM KCl (P < 0.01) cvere higher in young than in old animals . 3 The density (B-max) of alpha(1)-adrenoceptors and the dissociation constant (K-D) obtained in [H-3]-prazosin binding experiments were un changed by age. 4 The apparent affinity (pK(A)) and the percentage of functional receptors (qx100) remaining after phenoxybenzamine (0.03 mu M) were similar in both age groups. 5 After partial alpha(1)-adrenoce ptor inactivation with phenoxybenzamine, N-G-nitro-L-arginine methyles ter (30 mu M) significantly potentiated the E/[A] curve to noradrenali ne in young rats. However, only responses to 0.1 to 1 mu M noradrenali ne 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 mu M) contraction, with 1 mu M acetylc holine. 6 No modifications in the area (mu m(2)) or in the number of e ndothelial nuclei (per mm(2)) were observed between age groups. An elo ngation of the nuclei of endothelial cells was observed in the old ani mals. 7 These data suggest that the noradrenaline-induced contraction is decreased in old rats probably due to differences in either the con tractile machinery or postreceptor mechanisms. These alterations may b e accompanied by an impairment of the release or production of NO from endothelial cells.