Bradykinin-induced contraction of guinea pig lung in vitro

Lach, Estelle; Mousli, Marc; Landry, Yves; Gies, Jean-Pierre

doi:10.1007/bf00241097

Cited by 14 publications

(4 citation statements)

References 28 publications

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“…We found that HHcy significantly enhanced BK-induced constrictions of arterioles ( Figure 2A), which were likely due to an increased synthesis of PGH 2 / TxA 2 , as both indomethacin and SQ 29,548 substantially inhibited the responses, thereby eliminating the difference between HHcy and control arterioles (Figures 2B and 2C). Furthermore, the findings that the specific TxA 2 synthase inhibitor furegrelate 30 inhibited BK-induced constrictions and also eliminated the difference between responses in control and HHcy arterioles ( Figure 2D) indicate that TxA 2 is the primary constrictor prostaglandin synthesized to BK in arterioles of HHcy rats.…”

Section: Discussionmentioning

confidence: 88%

Simultaneously Increased TxA ₂ Activity in Isolated Arterioles and Platelets of Rats With Hyperhomocysteinemia

Ungvári

Sarkadi-Nagy

Bagi

et al. 2000

ATVB

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We aimed to elucidate the effect of hyperhomocysteinemia (HHcy) on the synthesis of prostaglandins in rat skeletal muscle arterioles and platelets. Male Wistar rats were divided into 2 groups: (1) control rats, with plasma Hcy levels of 6.5+/-0.5 micromol/L (n=50) and (2) rats with HHcy, induced by daily intake of 1 g/kg body weight methionine in the drinking water for 4 weeks (plasma Hcy levels were 20.6+/-3.0 micromol/L, P<0.01 versus controls; n=50). Arterioles (diameter approximately 130 micrometer) were isolated from the gracilis muscle, cannulated, and pressurized (at 80 mm Hg), and changes in their diameters were followed by video microscopy. Constrictions to bradykinin (BK; 10(-10) to 10(-7) mol/L) were significantly greater in HHcy than in control rat arterioles (at 10(-9) mol/L BK, changes were 11+/-3% in control and 41+/-9% in HHcy rats). The cyclooxygenase inhibitor indomethacin (10(-5) mol/L), the prostaglandin H(2)/thromboxane A(2) (PGH(2)/TxA(2)) receptor antagonist SQ 29,548 (10(-6) mol/L), or the TxA(2) synthase inhibitor furegrelate (5x10(-6) mol/L) significantly decreased constrictions to BK in both groups but more so in HHcy arterioles, thus eliminating the difference between responses of HHcy and control arterioles. Constrictions to U46619 (a TxA(2) analogue) were significantly greater in HHcy than in control arterioles (at 10(-8) mol/L U46619, values for controls were 33+/-2% and 54+/-3% for HHcy). Endothelium removal or indomethacin treatment attenuated constrictions to U46619 in HHcy arterioles and eliminated the difference in responses. Also, aggregation of platelets from HHcy rats to collagen and ADP was significantly enhanced compared with controls (with 5 microgram/mL collagen: controls, 23+/-5%; HHcy, 49+/-5%; with 10(-7) mol/L ADP: controls, 25+/-3%; HHcy, 35+/-3%). Indomethacin or SQ 29,548 caused greater inhibition of aggregation of HHcy platelets compared with controls, thereby eliminating the differences between the 2 groups. Thus, HHcy enhances TxA(2) synthesis both in the arteriolar endothelium and platelets. By promoting vascular constriction and platelet aggregation simultaneously, these alterations are likely to contribute to the atherothrombotic vascular diseases described in HHcy.

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Section: Discussionmentioning

confidence: 88%

Simultaneously Increased TxA ₂ Activity in Isolated Arterioles and Platelets of Rats With Hyperhomocysteinemia

Ungvári

Sarkadi-Nagy

Bagi

et al. 2000

ATVB

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“…Inconsistency between in vivo (Ricciardolo et al , 1994) and our in vitro results may reflect differences in de novo synthesis of kinins, although generation of kinins in airway preparations has been demonstrated (Farmer et al , 1994). It has also been shown in both guinea‐pig (Arakawa et al , 1992; Lach et al , 1994) and human (Molimard et al , 1994) airways that bradykinin exerts part of its effect through a pathway that is sensitive to indomethacin (a cyclo‐oxygenase inhibitor). Prostanoid synthesis may originate from the airway epithelium (Lindström et al , 1992), which could in part explain the divergent results obtained with our epithelium‐denuded preparations.…”

Section: Discussionmentioning

confidence: 99%

Neurokinin A‐LI release after antigen challenge in guinea‐pig bronchial tubes: influence of histamine and bradykinin

Lindström

Andersson

1997

British J Pharmacology

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1 Our aim was to determine if antigen challenge stimulates sensory nerves and provokes the release of tachykinins. The involvement of histamine and bradykinin was studied by using speci®c receptor antagonists. Capsaicin-induced responses were also examined. Experiments were performed in vitro on tracheal and bronchial preparations from ovalbumin-sensitized guinea-pigs. 2 Characterization of ovalbumin-induced contraction, with regard to histamine and bradykinin, was carried out on airway ring preparations in the presence of phosphoramidon. The histamine H 1 receptor antagonist pyrilamine reduced allergen-induced bronchial contractions by about 30%, whereas the bradykinin B 2 receptor antagonist icatibant (Hoe 140) did not signi®cantly aect the response. Combined treatment with pyrilamine (1 mM) and icatibant (0.1 mM) reduced the contractions by about 80%, indicating a synergistic inhibitory action. Tracheal preparations were not signi®cantly aected by treatments, neither were capsaicin-induced contractions. 3 To study the out¯ow of tachykinins, we used a perfused bronchial-tube preparation, allowing simultaneous measurement of smooth muscle tension and mediator release. Neurokinin A-like immunoreactivity (NKA-LI) and substance P-like immunoreactivity (SP-LI) were determined by radioimmunoassay. 4 The results of the perfusion study showed an increased out¯ow of NKA-LI into the perfusate in response to ovalbumin (127% of basal) challenge. SP-LI determined in some of the samples showed a much lower amount (40 to 70 times lower) of SP-LI than NKA-LI. Treatment with icatibant and pyrilamine, separately and in combination, signi®cantly reduced the ovalbumin-induced NKA-LI out¯ow by 38%, 26% and 22%, respectively. 5 Capsaicin-induced out¯ow (124% of basal) was not signi®cantly aected by treatments (icatibant 121%, pyrilamine 107% and combined treatment 111% of basal). However, when pyrilamine was present the increased out¯ow was not statistically signi®cant. 6 In conclusion, we found that allergen provocation of guinea-pig bronchi caused an increased out¯ow of NKA-LI that was reduced by treatment with both pyrilamine and icatibant. These ®ndings demonstrate that the allergen-induced release of histamine and bradykinin stimulate sensory nerves and thereby increase out¯ow of tachykinins that contribute to the allergic reaction.

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“…Although a NO-pathway has been described to be partly involved in bradykinin-induced tracheal relaxation (Schlemper and Calixto 1994) and to modulate bronchoconstriction in response to bradykinin (Belvisi et al 1992), the bradykinin-induced lung contraction (Lach et al 1994) appears to be unaffected by L-NAME. In addition, L-NAME did not significantly modify lung responsiveness to carbachol.…”

Section: Discussionmentioning

confidence: 99%

Bombesin-induced contractions of guinea pig lung strips are modulated by endogenous nitric oxide

Lach

Daeffler

et al. 1995

Naunyn-Schmiedeberg's Arch Pharmacol

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We have investigated the effects of a nitric oxide (NO) biosynthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the bombesin-evoked contraction of guinea pig parenchymal lung strips. The bombesin-induced contractions of lung strips were significantly increased after L-NAME (300 micro)) pre-treatment. The maximal response was increased (P < 0.01) by 37% after L-NAME treatment when compared with the control group. The pD2 value was not influenced by L-NAME pre-treatment. The enhancement of the bombesin-induced contraction caused by L-NAME was reversed by addition of an excess of the NO precursor L-arginine (600 microM) but not by the addition of its inactive enantiomer D-arginine (600 microM). Like L-NAME, methylene blue (1 microM), an agent that inhibits the soluble guanylyl cyclase activated by NO, significantly increased (P < 0.01) the maximal contraction induced by bombesin (183 +/- 16 mg) when compared with the control group (141 +/- 15 mg). When tested against other agonist-induced contractions, L-NAME did not change the responsiveness of parenchymal lung strips to bradykinin or carbachol but significantly increased lung contraction induced by histamine. NO synthesis inhibition resulted in a pronounced increase in the bombesin-induced contraction of guinea-pig lung strips. Our results suggest that bombesin contributes to NO synthesis and release which then acts to reduce the contraction of the lungstrip in response to bombesin.

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Bradykinin-induced contraction of guinea pig lung in vitro

Cited by 14 publications

References 28 publications

Simultaneously Increased TxA ₂ Activity in Isolated Arterioles and Platelets of Rats With Hyperhomocysteinemia

Simultaneously Increased TxA ₂ Activity in Isolated Arterioles and Platelets of Rats With Hyperhomocysteinemia

Neurokinin A‐LI release after antigen challenge in guinea‐pig bronchial tubes: influence of histamine and bradykinin

Bombesin-induced contractions of guinea pig lung strips are modulated by endogenous nitric oxide

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Bradykinin-induced contraction of guinea pig lung in vitro

Cited by 14 publications

References 28 publications

Simultaneously Increased TxA 2 Activity in Isolated Arterioles and Platelets of Rats With Hyperhomocysteinemia

Simultaneously Increased TxA 2 Activity in Isolated Arterioles and Platelets of Rats With Hyperhomocysteinemia

Neurokinin A‐LI release after antigen challenge in guinea‐pig bronchial tubes: influence of histamine and bradykinin

Bombesin-induced contractions of guinea pig lung strips are modulated by endogenous nitric oxide

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Resources

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Simultaneously Increased TxA ₂ Activity in Isolated Arterioles and Platelets of Rats With Hyperhomocysteinemia

Simultaneously Increased TxA ₂ Activity in Isolated Arterioles and Platelets of Rats With Hyperhomocysteinemia