CARDIAC ENDOTHELIN-1 CONTENT AND RECEPTOR SUBTYPE IN SPONTANEOUSLY HYPERTENSIVE RATS

Endothelin-1 (ET-1), a newly discovered peptide with potent vasoconstrictor and growth-promoting effects, has been implicated in high blood pressure and cardiac hypertrophy in the spontaneously hypertensive rat (SHR). In the present study, we measured plasma ET-1 levels and tissue ET-I concentrations in the four cardiac chambers of 17- to 18-week-old SHR and their normotensive controls, Wistar Kyoto (WKY) rats. SHR had slightly but significantly higher plasma ET-1 levels than WKY. The ventricles had the highest ET-1 content and the atria in both strains had the highest ET-1 concentrations. ET receptor subtypes were analysed by radiogand binding with ET-1, BQ-123 and IRL 1620 in crude membrane preparations of the four cardiac chambers. No differences in receptor subtype densities or affinities were apparent between the two strains. ET, represented 75 to 85% of both ET receptors. Competition analysis revealed that in both strains left ventricular tissue had lower receptor densities and higher affinities than the atria, These results suggest that ET-1 and its receptor although contributing in the maintenance of high blood pressure may not be an important factor during stable cardiac hypertrophy in adult SHR. The differential distribution of ET-1 content and receptor densities favoring the atria in both strains suggest that this peptide may have a different physiological role in the atria from that in the ventricles. (C) 1995 Academic Press Limited