ENDOTHELIN-INDUCED VASOCONSTRICTION AND RELEASE OF ATRIAL NATRIURETIC PEPTIDES IN THE RAT

Endothelin-I (ET-I) was given to male Sprague-Dawley rats in i.v. bolus injections to evaluate its effects on blood pressure and the release of atrial natriuretic peptides (ANP). In awake rats ET-I (0.3, 1 and 3 nmol kg-1 body wt) transiently reduced mean arterial pressure (MAP) and increased heart rate (HR), followed by a prolonged increase in MAP. The magnitude of these changes and the duration of the increase in MAP were dose-related. The increase in MAP was completely blocked by verapamil, reversed by sodium nitroprusside, slightly reduced by rat atrial natriuretic factor (103-126) and unaffected by saralasin. The initial fall in MAP was also unaltered by these agents. In all groups HR changes were mirror-images of MAP. In anaesthetized rats ET-I (1 nmol kg-1 body wt) induced a sustained release of ANP. Right atrial pressure increased transiently and then fell below baseline. When the increase in MAP was blocked with sodium nitroprusside, ET-I still produced an increase in ANP. In conclusion we find that repeated i.v. administration of ET-I induces immediate vasodilatation, without signs of tachyphylaxis, followed by long-lasting severe vasoconstriction. Baroreceptor function seems to be unchanged. ET-I appears to induce ANP release by a direct action on atrial myocytes, independent of right atrial and systemic arterial pressure. We hypothesize that endothelin may be a mediator of stretch-induced release of ANP.