Vascular effects of endothelin‐1 in the cat; modification by indomethacin and l‐NAME

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Abstract
Intravenous infusion of endothelin‐1 (ET‐1) in the cat, 60 pmol × kg body wt‐1x min‐1for 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 × kg body wt‐1x 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.