CARDIOVASCULAR EFFECTS OF LONG-TERM ENDOTHELIN INFUSION AND RESPONSES TO ENDOTHELIN DURING ACTH INFUSION IN CONSCIOUS SHEEP

被引:9
作者
MAY, CN
MATHAI, ML
MCDOUGALL, JG
WHITWORTH, JA
机构
[1] Howard Florey Institute of Experimental Physiology and Medicine University of Melbourne, Parkville
[2] Department of Medicine, St. George Hospital, University of New South Wales
基金
英国医学研究理事会;
关键词
CORTICOTROPIN; BLOOD PRESSURE; CARDIAC OUTPUT; ENDOTHELIN; SHEEP;
D O I
10.1093/ajh/6.10.837
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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 mug/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.
引用
收藏
页码:837 / 843
页数:7
相关论文
共 30 条
[21]  
Tresham J.J., Dusting G.J., Coghlan J.P., Et al., Haemodynamic and hormonal effects of N-nitro-L-arginine, an inhibitor of nitric oxide biosynthesis, in sheep, Clin Exp Pharmacol Physiol, 18, pp. 327-330, (1991)
[22]  
Tomita K., Ujiie K., Nakanishi T., Et al., Plasma endothelin levels in patients with acute renal failure, N Engl J Med, 321, (1989)
[23]  
Morel D.R., Lacroix J.S., Hemson A., Et al., Increased plasma and pulmonary lymph levels of endothelin during endotoxin shock, Eur J Pharmacol, 16, pp. 427-428, (1989)
[24]  
Rakugi H., Nakamaru M., Saito H., Et al., Endothelin inhibits renin release from isolated glomeruli, Bio- Chem Biophys Res Commun, 157, pp. 1164-1168, (1988)
[25]  
Fukuda J., Hirata Y., Yoshimi H., Et al., Endothelin is a potent secretagogue for atrial natriuretic peptide incultured rat atrial myocytes, Biochem Biophys Res Commun, 155, pp. 167-172, (1988)
[26]  
Valetin J.-P., Gardner D.G., Weidemann E., Et al., Modulation of endothelin effects on blood pressure and hematocrit by atrial natriuretic peptide, Hypertension, 17, pp. 86-869, (1991)
[27]  
Parkes D.G., Coghlan J.P., McDougall J.G., Et al., Longterm hemodynamic actions of atrial natriuretic factor (99-126) in conscious sheep, Am J Physiol, 254, pp. 811-815, (1988)
[28]  
Goetz K.L., Wang B.C., Madwed J.B., Et al., Cardiovascular, renal and endocrine responses to intravenous endothelin in conscious dogs, Am J Physiol, 255, pp. R1064-R1068, (1988)
[29]  
McDougall, Barnes J., Coghlan J.P., Et al., The effect of corticotrophin (ACTH) administration on the pressor action of angiotensin II, noradrenaline and tyramine in sheep, Clin Exp Pharmacol Physiol, 5, pp. 449-455, (1978)
[30]  
Coghlan J.P., Denton D.A., Graham W.F., Et al., Effect of ACTH administration on the haemodynamic response to arginine vasopressin in sheep, Clin Exp Pharmacol Physiol, 7, pp. 559-562, (1980)