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1. The aim of the present study was to investigate the effects of bradykinin and [des-Arg9]-bradykinin and their relaxant mechanisms in the mouse isolated trachea. 2. In the resting tracheal preparations with intact epithelium, bradykinin and [des-Arg9]-bradykinin (each drug, 0.01-10 microM) induced neither contraction nor relaxation. In contrast, bradykinin (0.01-10 microM) induced concentration-dependent relaxation when the tracheal preparations were precontracted with methacholine (1 microM). The relaxation induced by bradykinin was inhibited by the B2 receptor antagonist, D-Arg0-[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140, 0.01-1 microM) in a concentration-dependent manner whereas the B1 receptor antagonist, [des-Arg9,Leu8]-bradykinin (0.01-1 microM), had no inhibitory effect on bradykinin-induced relaxation. [des-Arg9]-bradykinin (0.01-10 microM) also caused concentration-dependent relaxation after precontraction with methacholine. The relaxation induced by [des-Arg9-bradykinin was concentration-dependently inhibited by the B1 receptor antagonist, [des-Arg9,Leu8]-bradykinin (0.01-1 microM), whereas the B2 receptor antagonist, Hoe 140 (0.01-1 microM) was without effect. 3. In the presence of the cyclo-oxygenase inhibitor, indomethacin (0.01-1 microM), the relaxations induced by bradykinin and [des-Arg9]-bradykinin were inhibited concentration-dependently. 4. Two nitric oxide (NO) biosynthesis inhibitors NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) and NG-nitro-L-arginine (L-NOARG, 100 microM) had no inhibitory effects on the relaxations induced by bradykinin and [des-Arg9]-bradykinin. Neither did the selective inhibitor of the soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM) inhibit the relaxations induced by bradykinin and [des-Arg9]-bradykinin. 5. Prostaglandin E2 (PGE2, 0.01-33 microM) caused concentration-dependent relaxation of the tracheal preparations precontracted with methacholine. Indomethacin (1 microM) and ODQ (10 microM) exerted no inhibitory effects on the relaxation induced by PGE2. 6. The NO-donor, sodium nitroprusside (SNP; 0.01-100 microM) also caused concentration-dependent relaxation of the tracheal preparations precontracted with methacholine. ODQ (0.1-1 microM) concentration-dependently inhibited the relaxation induced by SNP. 7. These data demonstrate that bradykinin and [des-Arg9]-bradykinin relax the mouse trachea precontracted with methacholine by the activation of bradykinin B2-receptors and B1-receptors, respectively. The stimulation of bradykinin receptors induces activation of the cyclo-oxygenase pathway, leading to the production of relaxing prostaglandins. The NO pathway is not involved in the bradykinin-induced relaxation. The relaxation caused by NO-donors in the mouse trachea is likely to be mediated via activation of soluble guanylate cyclase.

1. The influence of salt (sodium chloride; NaCl) (an additional 6% in the diet) and that of a novel sodium-reduced, potassium-, magnesium-, and L-lysine-enriched salt alternative on the cardiovascular effects of ramipril was studied in stroke-prone spontaneously hypertensive rats in a 6-week study. The intake of sodium chloride was adjusted to the same level by adding the salt alternative at a 1.75 times higher amount than regular salt. 2. Salt produced a marked rise in blood pressure and induced cardiac hypertrophy and significant mortality, while the salt alternative neither increased blood pressure nor caused any mortality and produced less cardiac hypertrophy than salt. 3. Ramipril treatment at a daily dose of 3 mg kg-1 normalized blood pressure and prevented the development of cardiac hypertrophy of rats on control diet. These effects of ramipril were blocked by the addition of salt but were only slightly attenuated by the addition of the salt alternative. The mortality in the salt group was prevented by ramipril. 4. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Salt, but not the salt alternative, increased vascular contractile responses to noradrenaline. Ramipril treatment improved the arterial relaxation responses to acetylcholine and to sodium nitroprusside. The vascular relaxation enhancing effect of ramipril was blocked by salt but only slightly attenuated by the salt alternative. 5. Ramipril treatment did not significantly increase plasma renin activity in the presence or in the absence of salt supplementation. The salt alternative did not cause hyperkalaemia, either alone or in combination with ramipril treatment. 6. Both salt supplementations, irrespective of ramipril treatment, induced a six to eight fold increase in the urinary excretion of calcium. There was an expected 90 to 140% rise in the urinary excretion of magnesium and 200% rise in the urinary excretion of potassium in the salt alternative group. Salt also produced an approximately 50% increase in magnesuria.7. Our findings suggest that replacement of salt by the potassium-, magnesium- and L-lysine-enriched salt alternative improves the cardiovascular effects of ramipril. In the present study the beneficial effect was related to the increased intakes of potassium and/or magnesium and L-lysine from the salt alternative because the amount of sodium chloride was the same.