Endothelin-1 pulmonary vasoconstriction in rats with diaphragmatic hernia.
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.
Published In/Presented At
Coppola, C. P., Au-Fliegner, M., & Gosche, J. R. (1998). Endothelin-1 pulmonary vasoconstriction in rats with diaphragmatic hernia. The Journal of surgical research, 76(1), 74–78. https://doi.org/10.1006/jsre.1997.5293
Medicine and Health Sciences | Pediatrics
Department of Pediatrics, Department of Surgery