Nitric oxide pathway‐mediated relaxant effect of bradykinin in the guinea‐pig isolated trachea

Abstract

1 The effects of two nitric oxide (NO) biosynthesis-inhibitors N0-nitro-L-arginine (L-NOARG) and N0-monomethyl-L-arginine (L-NMMA) on the relaxation induced by bradykinin (BK, 100 nM), isoprenaline (Iso, 1 lAM) and sodium nitroprusside (SNP, 1 lgM) were investigated in epithelium-intact strips of guinea-pig isolated trachea. 2 Relaxations induced by BK (100 nM) in guinea-pig tracheal strips under spontaneous tone were inhibited in a concentration-related manner by L-NOARG and L-NMMA (1 to 100 lM), with ICs (and 95% confidence limits) of 9.1 (6.9-11.6) lM and 7.0 (4.2-12.3) gM, respectively. However, at the maximal concentration (100 tM) used, neither of these drugs inhibited completely BK-induced relaxation (maximal inhibition of 74± 7 and 67± 7%, respectively). On the other hand, D-NMMA, the Denantiomer of L-NMMA, up to 100 gM failed to inhibit BK-induced relaxation. The relaxation induced by Iso (1 lM) and SNP (1 lM) were not affected by either L-NOARG or L-NMMA (30 lM). 7 These findings indicate that BK-induced relaxation in guinea-pig trachea is mediated jointly by the release of NO or a NO-related substance and a prostanoid, probably prostaglandin E2.

Involvement of B2 receptors in the bradykinin‐induced relaxation of guinea‐pig isolated trachea

“…The responses to melittin were unaffected by bradykinin antagonists (Figure 4) (0) [Melittin] (-log M) 6 and NPC 17761. In previous studies it had been suggested that bradykinin-induced relaxation was related to the presence of the epithelium (Bramley et al, 1990;Schlemper & Calixto, 1994). Bramley et al (1990) showed that in the presence of indomethacin the response of the guinea-pig tracheal preparation to bradykinin was changed from a relaxation to a contraction.…”

“…Intact tracheal preparations were allowed to develop a spontaneous tone. Treatment with indomethacin reduced the release of prostaglandins (Bramley et al, 1990) and the spontaneous tone (Schlemper & Calixto, 1994). Tracheal preparations without epithelium did not develop a spontaneous tone (Bramley et al, 1990).…”

“…effect (Bramley et al, 1990;Frossard et al, 1990;Schlemper & Calixto, 1994). However, Bramley et al (1990) noted that intact preparations (with epithelium) gained appreciable tone during the equilibration period, whereas rubbed trachea (without epithelium) developed no visible tone.…”

The mechanism of gentisic acid-induced relaxation of the guinea pig isolated trachea: the role of potassium channels and vasoactive intestinal peptide receptors

“…The trachea was rapidly removed, freed from connective tissue, and cut into six transverse rings (3-4 mm wide), each containing 3 cartilages as described previously (12,13). The rings were opened (usually 6 strips of 8-10 mm in length were obtained from the same animal) and suspended in individual 10-ml jacketed organ baths containing KrebsHenseleit solution maintained at 37 o C, pH 7.2, gassed with a mixture of 95% O 2 and 5% CO 2 .…”

“…In some experiments, the epithelial layer of the trachea was gently removed with a cotton-tipped applicator. The integrity of the epithelium was assessed by the ability of bradykinin to induce relaxation (12).…”