Mechanisms of noradrenaline-induced vasorelaxation in isolated femoral arteries of the neonatal rat

Abstract

Isolated arteries from the femoral circulation of Wistar rats mounted on a small vessel myograph demonstrated age related tension development to noradrenaline (NA, 1 x 10(-8) - 5 x 10(-5) M) day 20 greater than day 10 (P<0.005); day 100 greater than day 20 (P<0.001) and depolarizing potassium (125 mM) buffer day 20 greater than day 10 (P<0.001). NA evoked dilatation in femoral arteries from neonatal rats (10 days) when added to unstimulated vessels or to those preconstricted with the thromboxane mimetic, U46619. Relaxation to NA was inhibited by L-NAME (0.1 mM) (P<0.001), endothelial removal (P<0.001) and the alpha2-adrenoceptor antagonist, yohimbine (0.1 microM) (P<0.001). Alpha1- or beta-adrenoceptor antagonism was without effect. Relaxation was evoked in femoral arteries of the 10-day-old rats by the alpha2-adrenoceptor agonist UK14304 (1 x 10(-8) - 5 x 10(-5) M). This relaxation was also abolished by L-NAME (0.1 mM) (P<0.001) or endothelial removal (P<0.001). Alpha2-adrenoceptor-mediated vasorelaxation was the predominant response to NA stimulation in femoral arteries of the neonatal rat. These responses were endothelium-dependent and were NO-mediated.

Figure 1

(a) Tension development to noradrenaline (NA) in femoral arteries (day 10 and 20) and branches of the femoral artery (day 100 and 200). Values are given as mean±s.e.mean. ^*P < 0.005 for maximum tension, day 10 vs day 20; ^**P < 0.001 for maximum tension, day 20 vs day 100. (b) The effect of N^ω-nitro L-arginine methyl ester (L-NAME, 0.1 mM) and endothelial removal on NA-induced vasorelaxation in isolated femoral arteries of 10-day-old rats. Data are expressed as percentage relaxation of pre-constricted tone induced by 9,11-Dideoxy-11_α,9_α-epoxy-methanoprostaglandin F_2α (U46619, 1 μM). Values are given as mean±s.e.mean. ^**P < 0.001 by ANOVA; control vs L-NAME and control vs endothelial removal. (c) The effect of adrenoceptor antagonists on NA-induced vasorelaxation in isolated femoral arteries of 10-day-old rats. Prazosin: 0.1 μM; Yohimbine: 0.1 μM; Atenolol: 5 μM; ICI118551 (1-[2,3-(Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol); 0.1 μM. Data are expressed as percentage relaxation of pre-constricted tone induced by U46619 (1 μM). Values are given as mean±s.e.mean. ^**P < 0.001; control vs yohimbine (by ANOVA) and control vs prazosin (maximum relaxation, by t-test). (d) Vasorelaxation to 5-Bromo-N-[2-imidazolin-2-yl]-6-quinoxalinamine (UK14304) in isolated femoral arteries of 10-day-old rats and the effect of L-NAME (0.1 mM) and endothelial removal on UK14304-induced vasorelaxation. Data are expressed as percentage relaxation of pre-constricted tone induced by U46619 (1 μM). Values are given as mean±s.e.mean. ^**P < 0.001 by ANOVA; control vs L-NAME and control vs endothelial removal.

Figure 2

(a) Vasoconstriction to phenylephrine in isolated femoral arteries of 10-day-old rats. Data are expressed as a percentage of the response to 125 mM KCl. Values are given as mean±s.e.mean. (b) Vasorelaxation to isoprenaline in isolated femoral arteries of 10-day-old rats. Data are expressed as percentage relaxation of pre-constricted tone induced by U46619 (1 μM). Values are given as mean±s.e.mean.)