Effects of nitric oxide synthase inhibitors, l-NG-nitroarginine and l-NG-nitroarginine methyl ester, on responses to vasodilators of the guinea-pig coronary vasculature (original) (raw)

on vasodilatation induced by ATP, substance P, 5-hydroxytryptamine (5-HT), bradykinin and sodium nitroprusside (SNP) were examined in the guinea-pig coronary bed, by use of a Langendorff technique. The effects of these inhibitors of nitric oxide synthesis were assessed on their ability to inhibit both the amplitude and the area of the vasodilator response. 2 The vasodilator responses evoked by low doses of 5-HT (5 x 10`-'°5 x 10 mol) were almost abolished by L-NAME and L-NOARG (both at 10-5, 3 x 10-5 and 1O-4M), although L-NOARG (3 x 10-s M) was significantly less potent than L-NAME (3 x 10-5 M) as an inhibitor of vasodilator responses to 5-HT (5 x 10-8 mol). 3 The vasodilator responses evoked by substance P (5 x 102-5 X I0-mol) were reduced in the presence of L-NAME and L-NOARG (both at 10-5 and 3 x 10-5 M). The response to substance P was almost abolished by L-NAME and L-NOARG (both at 10-4 M). 4 The amplitude of the vasodilator responses to ATP (5 x 10-" and 5 x 10-9-5 x 10-mol) was little affected by either L-NAME or L-NOARG (both at 10-5, 3 x 10-5 and 10-4 M). However, the area of the response to ATP (5 x 10-`o-5 x 10-7 mol) was inhibited by L-NAME (10-5, 3 x 10-5 and 10-4M) and to a lesser extent by L-NOARG (10-5 and 10-M). 5 The amplitude and area of the vasodilator responses to bradykinin (5 x 10-12-5 x 10-11 mol) were reduced, but not abolished, by L-NOARG and L-NAME. 6 Neither the amplitude nor area of the responses to sodium nitroprusside (5 x 10-'°-5 x 10-7 mol) were inhibited by either L-NAME or L-NOARG (both at 10-5 and 3 x 10-5 M). 7 It is concluded that in the guinea-pig coronary vasculature, the vasodilatation evoked by substance P and low doses of 5-HT is mediated almost exclusively via nitric oxide, whereas the vasodilatations evoked by ATP and bradykinin appear to involve other mechanisms in addition to the release of nitric oxide. L-NAME was a more effective agent than L-NOARG in inhibiting the vasodilator actions of 5-HT and ATP in this preparation.