Lw. Hunter et al., 6-Nitronorepinephrine has reduced activity at vascular adrenoceptors compared to norepinephrine, BIOG AMINE, 15(6), 2000, pp. 613-626
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.