Cardiovascular effects of long-term endothelin infusion and responses to endothelin during ACTH infusion in conscious sheep.
Infusion of endothelin-1 (ET-1) (2000 pmol/h) into conscious sheep for 6 days caused a sustained increase in mean arterial pressure (MAP) of 19 +/- 1 mm Hg. This response was mediated by the vasoconstrictor effect of ET-1 and was accompanied by a fall in cardiac output. Plasma renin concentration fell throughout the infusion and atrial natriuretic peptide was increased on day 1 of ET-1 infusion. Hematocrit dramatically increased, probably mainly due to plasma loss resulting from the ET-1-induced increased capillary hydrostatic pressure. To determine whether increased pressor responsiveness to ET-1 played a role in the rise in MAP caused by corticotropin (ACTH), the responses to bolus doses of ET-1 were evaluated before ACTH and on days 3 and 5 of ACTH infusion (5 micrograms/kg/day). ACTH increased MAP from 71 +/- 2 to 87 +/- 3 mm Hg. On the control day ET-1 (400, 1200, and 2000 pmol) increased MAP by 5 +/- 1, 18 +/- 6 and 35 +/- 11 mm Hg, respectively. No initial vasodilation occurred. The responses to all doses of ET-1 were similar during ACTH infusion. Plasma levels of ET-1 did not increase during ACTH infusion. These results demonstrate that long-term infusion of ET-1 caused a sustained increase in blood pressure. There was no evidence that the sensitivity or responsiveness to ET-1 were altered during infusion of ACTH. In conclusion, ET-1 could play a role in the pathogenesis of hypertension but does not appear to be involved in the increase in blood pressure caused by ACTH.
May
C N
CN
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Australia.
Mathai
M L
ML
McDougall
J G
JG
Whitworth
J A
JA
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003243:Consciousness; D016232:Endothelins / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D012756:Sheep
D016232:Endothelins; D000324:Adrenocorticotropic Hormone