Coronary vasoconstriction to endothelin-1 increases with age before and after ischaemia and reperfusion

Objective: Ageing is known to be associated with changes within the heart. We investigated whether the coronary response to endothelin-1 (ET) and sara fotoxin S6c (S6c) is altered with increasing age, before and after cardiopl egic arrest. Methods: Using an isolated rat heart model, increasing concent rations of ETT and S6c were administered to rats of different ages (group I =one month; group II-five months; group III=21 months). An identical series of experiments was performed following the addition of indomethacin and N- G-nitro-L-arginine methyl ester (L-NAME) to the Krebs perfusion fluid. In a third series of experiments, increasing doses of ET-I were added to hearts following 4 h of cardioplegic arrest at 4 degrees C. Results: Coronary how s are expressed as a percentage of initial coronary flow+/-SEM. There was a greater decrease in coronary flow in the older rats for all doses of ET-1. ET-I (10(-9) M) reduced coronary flows to 72.8+/-3.7, 53.2+/-6.7 and 56.5/-10.7% for groups I-Ill respectively (P=0.01 I vs. Ii; P=0.1 I vs. III). A similar response to ET-I was seen in hearts perfused with indomethacin and L-NAME when compared to those perfused without (P=NS) Perfusion with ET-I (10(-9) M) following 4 h of cardioplegic arrest reduced coronary flows to 4 0.5+/-4.9, 26.8+/-4.8 and 24.1+/-3.9%, respectively (P=0.08 I vs. II; P=0.0 3 I vs. III). Perfusion with S6c (10(-10) NI) produced coronary flows of 93 .3+/-5.5, 77.0+/-3.5 and 73.9+/-3.9% for groups I-Ill, respectively (P=0.03 I vs. II; P=0.01 I vs. III). Perfusion with S6c (10(-9) M) in the presence of L-NAME and indomethacin reduced coronary hows to 85.7+/-3.0, 81.6+/-2.2 and 74.6+/-3.6% (P=NS I vs. Il; P=0.03 I vs. III). Conclusions: The corona ry vasoconstrictor response to ET-I and S6c increases with age. The increas ed vasoconstriction in response to ET-I is independent of the decrease in N O release seen with ageing. (C) 1999 Published by Elsevier Science B.V. All rights reserved.