Gene expression of endothelin isoforms and receptors in endothelin-1 knockout mice.

Gene expression of endothelin (ET) isoforms and receptors was examined in ET-1 knockout mice and compared with that of wild-type mice. ET-1 mRNA and peptide levels were in parallel with the number of Edn1 authentic alleles. ET-2 mRNA levels in intestine and ET-3 mRNA and/or peptide levels in lung, brain, and intestine were not different among Edn1+/+ wild-type, Edn1+/- heterozygous, and Edn1-/- homozygous mice. ET(A) and ETB receptor mRNA levels in several organs also were not different among Edn1+/+ wild-type, Edn1+/- heterozygous, and Edn1-/- homozygous mice. These results suggest that gene expression of ET-2, ET-3, and ET(A/B) receptors is not affected by levels of ET-1 production and is regulated independently. Neither compensation by redundant expression of other ET isoforms nor upregulation of ET receptors could explain the elevated blood pressure in Edn1+/- heterozygous mice.