Abstract
The release of endogenous vasoconstrictors together with changes in the vascular responses are central to the pathophysiology of sepsis. The effects of in vitro incubation for 20 h with heat-killed group B Streptococcus (GBS, 3 × 107 colonyforming units mL-1) on the vasoconstrictor responses to noradrenaline (NA, 10-8 to 10-4 M), the thromboxane A2 analog 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α(U46619; 10-10 M to 10-6 M) and endothelin-1 (ET-1, 10-11 to 3 × 10-9 M) were evaluated on isolated intrapulmonary and mesenteric arteries from 10-17-d-old piglets. The incubation with GBS reduced the maximal contractile response to NA and ET-1 (p < 0.01) in both arteries. The nitric oxide (NO) synthase (NOS) inhibitorNω-nitro-L-arginine methyl ester (L-NAME; 10-4 M) completely reversed this hyporesponsiveness. GBS-treated mesenteric arteries also showed a significant reduction of the maximal contractions induced by U46619 (p < 0.05) and this effect was inhibited by 10-4 M L-NAME. In contrast, the maximal contractile responses to U46619 were similar in control and in GBS-treated pulmonary arteries. Addition of L-NAME did not modify the contractile responses to U46619 in GBS-treated pulmonary arteries. In conclusion, GBS-treated systemic arteries from neonatal piglets showed decreased responses to NA, U46619, and ET-1 due to enhanced NO release. GBS-treated pulmonary arteries also exhibited decreased responses to NA and ET-1 but not to U46619. Induction of NOS in vascular smooth muscle may play a key role in the hypotension and loss of systemic vascular responsiveness that occurs in GBS sepsis. The absence of pulmonary hyporesponsiveness to U46619 may partially explain the coexistence during sepsis of pulmonary hypertension and lung NOS induction.
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Abbreviations
- GBS:
-
Group B Streptococcus
- LPS:
-
lipopolysaccharide
- ET-1:
-
endothelin-1
- TXA2:
-
thromboxane A2
- NO:
-
nitric oxide
- iNOS:
-
inducible nitric oxide synthase
- NA:
-
noradrenaline
- U46619:
-
9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α
- L-NAME:
-
Nω-nitro-L-arginine methyl ester
- cfu:
-
colony-forming units
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Acknowledgements
The authors are grateful to Dr. Romero and Dr. Elorza for providing heat-killed GBS and to C. Rivas, R. Vara, and M. R. Gaítan for excellent technical assistance.
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Supported by a CICYT (SAF 96/0042) and FIS Grants (95/0308 and 95/0318) Grants. E. Villamor is a recipient of the Asociación Espanola de Pediatría/Arbora S.A. Grant for Pediatric Research.
Presented at the 1st European Congress of Pharmacology (EPHAR) and the 65th Annual Meeting of the Society for Pediatric Research, Washington, DC.
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Villamor, E., Pérez-Vizcaíno, F., Tamargo, J. et al. Effects of Group B Streptococcus on the Responses to U46619, Endothelin-1, and Noradrenaline in Isolated Pulmonary and Mesenteric Arteries of Piglets. Pediatr Res 40, 827–833 (1996). https://doi.org/10.1203/00006450-199612000-00009
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DOI: https://doi.org/10.1203/00006450-199612000-00009
