AGING AND IN-VITRO VASCULAR-RESPONSES TO ENDOTHELIN-1 IN SEVERAL RAT STRAINS

The endothelins are a recently discovered family of potent contractile peptides produced by endothelial cells. These peptides have been suggested to play an important role in the pathogenesis of hypertension, myocardial infarction, cardiogenic shock, and so on. The aim of our study was to compare the responses to endothelin-1 (ET-1) with those to L-noradrenaline (NA) in aortic rings from rats of different strains and ages. Thoracic aorta rings from spontaneously hypertensive (SHR), Wistar Kyoto (WKY), Brown Norway (BN) and spontaneously hyperlipemic (Yoshida, YOS) rats 2-4 (young), 6-8 (adult) and 20-25 (old) months old were used. There were no changes in the pD2 values for ET-1 and NA between WKY and SHR rats at the ages studied. The ET-1 and NA Emax in adult SHR rats was significantly lower than in the age-matched WKY animals. Old age reduced the ET-1 and NA Emax in both SHR and WKY rats abolishing the difference observed at 6-8 months in the same groups. The reactivity to ET-1 and NA of BN and YOS rats was modified only in young rats. In YOS strain aging did not modify the ET-1 and NA responses as the pD2 and Emax values remained unchanged. Our findings demonstrate that ET-1 is a more potent vasoconstrictor than NA and that this potency remains unchanged throughout the ages and the pathologies studied. In contrast, the pD2 of NA decreases with old age in SHR and WKY rats. We conclude that rat strain but not hypertension or hyperlipemia can modify the response to ET-1 or NA in old age. We suppose that this functional change may involve alterations in the responsiveness of vascular smooth muscle. © 1993 The Italian Pharmacological Society.