VASCULAR EFFECTS OF ENDOTHELIN-1 IN THE CAT - MODIFICATION BY INDOMETHACIN AND L-NAME

Intravenous infusion of endothelin-1 (ET-1) in the cat, 60 pmol x kg body wt-1 x min-1 for 5 min, induced an increase in mean arterial blood pressure (MAP) of 41.3 +/- 4.8 mmHg (n = 6; P < 0.001). Blood flow, as determined with radioactive microspheres, was reduced in many tissues. Reductions by 70-80% were observed in the choroid plexus, pineal and pituitary glands. Total cerebral blood flow was reduced by 18-23%. Pre-treatment with indomethacin or a combination of indomethacin and L-NAME caused vasoconstriction in many tissues and modified the responses to ET-1 in a variable way, suggesting that normally, ET-1 tends to release arachidonic acid metabolites and nitric oxide with great variations between different tissues. Intracerebroventricular infusion (i.c.v.) of ET-1, 10 pmol x kg body wt-1 x min-1, caused an increase in MAP of 79 +/- 11 mmHg (n = 6; P < 0.001). Regional blood flow in the medulla oblongata, medulla spinalis, choroid plexus, pineal and pituitary glands was reduced by 60-80%. Heart rate, cardiac output and coronary blood flow were significantly increased after 30 min i.c.v. infusion, indicating an activation of the heart, most probably as part of a central ischaemic response. Our results indicate that in many tissues the vasoconstrictive effect of ET-1 is influenced by indomethacin- and L-NAME-sensitive vasodilator mechanisms that are activated by the peptide. In the CNS, there may be marked effects on regional blood flow after i.c.v. infusion.