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-l ha s been implicated as a mediator of pulmonary hypertension. ET-A recept ors are increased in the nitrofen model of CDH in rats. We hypothesize d that vasoconstrictor responses to endothelin-l are increased in pulm onary arterioles of rats with nitrofen-induced CDH. ' Materials and me thods. CDH was induced in fetal rats by feeding nitrofen (2,4-dichloro phenyl-p-nitrophenyl ether) to pregnant rats at midgestation. Third-ge neration pulmonary arterioles were isolated on the final day of gestat ion. Arterioles were cannulated and perfused at constant pressure with a physiologic salt solution. Diameters of arterioles from control ani mals (n = 8), CDH animals (n = 5), and animals exposed to nitrofen but without CDH (n = 4) were measured. Responses to endothelin-1 concentr ations of 10(-12) to 10(-8) M were compared by Student's t test. Resul ts. CDH arterioles constricted more than controls in response to endot helin-l 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 concentr ation of endothelin-l that induced half-maximal response (ED50) was lo wer 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 t o nitrofen but without CDH were not different from controls (P greater than or equal to 0.05). Conclusions. Exaggerated vasoconstrictor resp onses to endothelin-1 may contribute to pulmonary hypertension in CDH. (C) 1998 Academic Press.