UP-REGULATION OF A NON-ET(A) RECEPTOR IN HUMAN ARTERIES IN-VITRO

Receptor turnover may be a crucial part in the physiology of endotheli n (ET). Incubation of vessel segments could be a possible method to de monstrate this. The aim was to study contractile responses of human om ental arteries to different ET agonists at various periods after incub ation at 37 degrees C in 5% CO2 and air. The maximum effect (E(max); p ercentage of contraction to 60 mM K+ buffer solution) and the potency of ET-1 were unaltered (pD(2) = 8.82 +/- 0.06). The selective ET(B) ag onist IRL 1620 demonstrated a negligible E(max) in nonincubated seg se gments (2.4 +/- 0.9%). After only 1 day of incubation the E(max) was 5 1 +/- 23%, and it reached 114 +/- 53% after 5 days. The pD(2) of IRL 1 620 was stable throughout the incubation time (7.23 +/- 0.08). ET-3 sh owed a moderate E(max) in nonincubated segments (55 +/- 18%), with a p D(2) of 6.68 +/- 0.24. However, subsequent incubation revealed an incr ease of pD(2) to 8.60 +/- 0.20 on the fifth day. The maximum contracti on increased to 206 +/- 44%; this is equal to the contraction obtained in paired experiments with ET-1 (215 +/- 18%). These findings indicat e modulation of endothelin receptor expression after incubation of ves sel segments, and suggest the gradual appearance of a non-ET(A) recept or.