6-Nitronorepinephrine has reduced activity at vascular adrenoceptors compared to norepinephrine

The effectiveness of 6-nitronorepinephrine in contracting peripheral blood vessels via alpha(1) and alpha(2) adrenoceptors located on smooth muscle wa s studied. Concentration-response curves to 6-nitronorepinephrine and to no repinephrine were done in vitro using endothelium-free rings of canine femo ral artery and saphenous vein. Contraction mediated by alpha(1) receptors w as determined in femoral artery rings in the presence of rauwolscine (1 mu M), an alpha(2) receptor inhibitor, whereas contraction mediated by alpha(2 ) receptors was determined in proximal saphenous vein rings exposed to praz osin (1 mu M), an alpha(1) inhibitor. In the artery, the PD2 value at alpha (1) receptors was 6.2 +/- 0.3 for norepinephrine and 3.9 +/- 0.2 for 6-nitr onorepinephrine. Inhibition of alpha(1) receptors with prazosin significant ly shifted the 6-nitronorepinephrine curve rightward. In the alpha(2) model , the pD(2) for norepinephrine was 6.5 +/- 0.1, and for 6-nitronorepinephri ne was 4.4 +/- 0.1, with alpha(2) inhibition significantly shifting the 6-n itronorepinephrine curve, further to the right. HPLC analysis indicated the norepinephrine content to be 339 +/- 27 pmol/100 mg in femoral artery and 789 +/- 57 pmol/100 mg in saphenous vein, whereas 6-nitronorepinephrine was undetectable in either vessel. These results demonstrate that nitration of norepinephrine substantially reduces its capacity to contract canine blood vessels via alpha(1) or alpha(2) adrenoceptors located on smooth muscle.