ENDOGENOUS SYNTHESIS OF ENDOTHELIN-1 MAY MEDIATE A DELAYED PRESSER RESPONSE AFTER INJECTION OF ENDOTHELIN-1 IN RATS

We previously described delayed presser response (DPR) 3 h after endot helin (ET)-1 injection in normotensive rats. In the current study, we examined effects of the ET(A) receptor antagonist BQ123 (0.01 mu mol/k g/min intravenously, i.v.), phosphoramidon (100 mu mol/ kg i.v.), the neutral endopeptidase inhibitor SQ28603 (112 mu mol/kg + 0.04 mu mol/k g/min i.v.), the angiotensin-converting enzyme inhibitor enalaprilat ( 10 mu mol/kg i.v.), and the thromboxane receptor antagonist, SQ29548 ( 0.5 mu mol/kg + 0.5 mu mol/kg/h i.v.) on DPR. Vehicle and ET-1 (1.0 nm ol/kg i.v.) were administered on day 1; vehicle or drug and ET-1 were administered on day 2. BQ123 inhibited DPR 36% (vehicle 44 +/- 5, BQ12 3 28 +/- 3 mm Hg); phosphoramidon inhibited DPR 56% (vehicle 45 +/- 4, and phosphoramidon 20 +/- 5 mm Hg). DPR was unchanged after SQ28603 ( vehicle 39 +/- 2 and SQ28603 44 +/- 2 mm Hg), enalaprilat (vehicle 39 +/- 2 and enalaprilat 38 +/- 7 mm Hg), or SQ29548 (vehicle 46 +/- 6 an d SQ29548 43 +/- 3 mm Hg). The results suggest that DPR 3 h after ET-1 injection in rats is mediated in part through ET(A) receptors. DPR do es not appear to involve thromboxane or synthesis of angiotensin II (A II), but may be related to synthesis of ET-1.