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

Amanda Vials, Geoffrey Burnstock

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26 Citations (Scopus)

Abstract

The effects of l‐NG‐nitroarginine (l‐NOARG) and l‐NG‐nitroarginine methyl ester (l‐NAME) 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. The vasodilator responses evoked by low doses of 5‐HT (5 × 10−10−5 × 10−8 mol) were almost abolished by l‐NAME and l‐NOARG (both at 10−5, 3 × 10−5 and 10−4 m), although l‐NOARG (3 × 10−5 m) was significantly less potent than l‐NAME (3 × 10−5 m) as an inhibitor of vasodilator responses to 5‐HT (5 × 10−8 mol). The vasodilator responses evoked by substance P (5 × 10−12−5 × 10−9 mol) were reduced in the presence of l‐NAME and l‐NOARG (both at 10−5 and 3 × 10−5 m). The response to substance P was almost abolished by l‐NAME and l‐NOARG (both at 10−4 m). The amplitude of the vasodilator responses to ATP (5 × 10−11 and 5 × 10−9−5 × 10−7 mol) was little affected by either l‐NAME or l‐NOARG (both at 10−5, 3 × 10−5 and 10−4 m). However, the area of the response to ATP (5 × 10−10‐5 × 10−7 mol) was inhibited by l‐NAME (10−5, 3 × 10−5 and 10−4 m) and to a lesser extent by l‐NOARG (10−5 and 10−4 m). The amplitude and area of the vasodilator responses to bradykinin (5 × 10−12−5 × 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 × 10−10−5 × 10−7 mol) were inhibited by either l‐NAME or l‐NOARG (both at 10−5 and 3 × 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. 1992 British Pharmacological Society

Original languageEnglish
Pages (from-to)604-609
Number of pages6
JournalBritish Journal of Pharmacology
Volume107
Issue number2
DOIs
Publication statusPublished - Oct 1992

Keywords

  • Nitric oxide synthase
  • blood vessels
  • coronary vasculature
  • l‐N‐nitroarginine
  • l‐N‐nitroarginine methyl ester
  • relaxation of smooth muscle

ASJC Scopus subject areas

  • Pharmacology

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