Article date: September 2002
By: Giuseppe Rossoni, Barbara Manfredi, Piero Del Soldato, Ferruccio Berti in Volume 137, Issue 2, pages 229-236
The ability of the nitric oxide (NO)‐releasing aspirin, NCX 4016, to control vasoconstrictor responses induced by electrical field stimulation (TNS) or by exogenous norepinephrine (NE) was investigated in perfused rat tail artery with intact endothelium.
NCX 4016 (25, 50 and 100 μM) dose‐dependently antagonized the vasoconstriction caused by TNS (from 0.5 to 64 Hz) and by NE (from 0.01 to 10 μM). The vasorelaxant activity of NCX 4016 (100 μM) in NE‐precontracted arteries was concomitant with a marked increase of tissue cyclic GMP (4.9 fold, P<0.001) and was significantly antagonized by the inhibitors of soluble guanylate cyclase, methylene blue and 1H‐[1,2,4]Oxadiazolo[4,3‐a]quinoxalin‐1‐one.
The effect of NCX 4016 was endothelium NO‐independent since, in preparations perfused with NG‐monomethyl‐L‐arginine (10 μM), this compound prevented the rise in basal perfusion pressure and reversed the accentuation of vasoconstrictor responses caused by NO synthase inhibition.
Aspirin‐moiety released by NCX 4016 inhibited the 6‐keto‐PGF1α formation without interfering with the vasorelaxant activity of NCX 4016, while aspirin (100 μM) was devoid of any activity against vasoconstriction induced by both TNS and NE in perfused rat tail artery.
NCX 4016 moderated adrenergic vasoconstriction in perfused rat tail arteries by a direct donation of NO without involving the relaxant factors such as PGI2 and NO from endothelial cells.
The results obtained with NCX 4016 in perfused rat tail artery bears some therapeutical potential in conditions associated with vascular smooth muscle hyperreactivity to adrenergic stimulation.
The ability of the nitric oxide (NO)‐releasing aspirin, NCX 4016, to control vasoconstrictor responses induced by electrical field stimulation (TNS) or by exogenous norepinephrine (NE) was investigated in perfused rat tail artery with intact endothelium.
NCX 4016 (25, 50 and 100 μM) dose‐dependently antagonized the vasoconstriction caused by TNS (from 0.5 to 64 Hz) and by NE (from 0.01 to 10 μM). The vasorelaxant activity of NCX 4016 (100 μM) in NE‐precontracted arteries was concomitant with a marked increase of tissue cyclic GMP (4.9 fold, P<0.001) and was significantly antagonized by the inhibitors of soluble guanylate cyclase, methylene blue and 1H‐[1,2,4]Oxadiazolo[4,3‐a]quinoxalin‐1‐one.
The effect of NCX 4016 was endothelium NO‐independent since, in preparations perfused with NG‐monomethyl‐L‐arginine (10 μM), this compound prevented the rise in basal perfusion pressure and reversed the accentuation of vasoconstrictor responses caused by NO synthase inhibition.
Aspirin‐moiety released by NCX 4016 inhibited the 6‐keto‐PGF1α formation without interfering with the vasorelaxant activity of NCX 4016, while aspirin (100 μM) was devoid of any activity against vasoconstriction induced by both TNS and NE in perfused rat tail artery.
NCX 4016 moderated adrenergic vasoconstriction in perfused rat tail arteries by a direct donation of NO without involving the relaxant factors such as PGI2 and NO from endothelial cells.
The results obtained with NCX 4016 in perfused rat tail artery bears some therapeutical potential in conditions associated with vascular smooth muscle hyperreactivity to adrenergic stimulation.
British Journal of Pharmacology (2002) 137, 229–236. doi:10.1038/sj.bjp.0704869
DOI: 10.1038/sj.bjp.0704869
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