Endothelin-1 pulmonary vasoconstriction in rats with diaphragmatic hernia.

Autor: Coppola CP; Section of Pediatric Surgery, Yale University School of Medicine, New Haven, Connecticut 06510, USA., Au-Fliegner M, Gosche JR
Jazyk: angličtina
Zdroj: The Journal of surgical research [J Surg Res] 1998 Apr; Vol. 76 (1), pp. 74-8.
DOI: 10.1006/jsre.1997.5293
Abstrakt: Background: Pulmonary hypertension is an important cause of mortality in infants with congenital diaphragmatic hernia (CDH). Endothelin-1 has been implicated as a mediator of pulmonary hypertension. ET-A receptors are increased in the nitrofen model of CDH in rats. We hypothesized that vasoconstrictor responses to endothelin-1 are increased in pulmonary arterioles of rats with nitrofen-induced CDH.
Materials and Methods: CDH was induced in fetal rats by feeding nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) to pregnant rats at midgestation. Third-generation pulmonary arterioles were isolated on the final day of gestation. Arterioles were cannulated and perfused at constant pressure with a physiologic salt solution. Diameters of arterioles from control animals (n = 8), CDH animals (n = 5), and animals exposed to nitrofen but without CDH (n = 4) were measured. Responses to endothelin-1 concentrations of 10(-12) to 10(-8) M were compared by Student's t test.
Results: CDH arterioles constricted more than controls in response to endothelin-1 at concentrations of 10(-11) M (29 +/- 11% vs 5 +/- 3%, P = 0.02) and 10(-10) M (40 +/- 14% vs 9 +/- 6%, P = 0.04). The log concentration of endothelin-1 that induced half-maximal response (ED50) was lower for CDH arterioles than for control arterioles (-10.3 +/- 0.6 vs -9.1 +/- 0.2, P = 0.03). Responses of arterioles from animals exposed to nitrofen but without CDH were not different from controls (P > or = 0.05).
Conclusions: Exaggerated vasoconstrictor responses to endothelin-1 may contribute to pulmonary hypertension in CDH.
Databáze: MEDLINE
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