Hoagland T M, Weaver L, Conlon J M, Wang Y, Olson K R
Indiana University School of Medicine, South Bend Center for Medical Education, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Am J Physiol Regul Integr Comp Physiol. 2000 Feb;278(2):R460-8. doi: 10.1152/ajpregu.2000.278.2.R460.
The cardiovascular effects of endothelin (ET)-1 and the recently sequenced homologous trout ET were examined in unanesthetized trout, and vascular capacitance curves were constructed to evaluate the responsiveness of the venous system to ET-1. A bolus dose of 667 pmol/kg ET-1 doubled ventral aortic pressure; produced a triphasic pressor-depressor-pressor response in dorsal aortic pressure (P(DA)); increased central venous pressure, gill resistance, and systemic resistance; and decreased cardiac output, heart rate, and stroke volume. These responses were dose dependent. Bolus injection of trout ET (333 or 1,000 pmol/kg) produced essentially identical, dose-dependent cardiovascular responses as ET-1. Dorsal aortic infusion of 1 and 3 pmol. kg(-1). min(-1) ET-1 and central venous infusion into the ductus Cuvier of 0.3 and 1 pmol. kg(-1). min(-1) produced similar dose-dependent cardiovascular responses, although the increase in P(DA) became monophasic. The heightened sensitivity to central venous infusion was presumably due to the more immediate exposure of the branchial vasculature to the peptide. Infusion of 1 pmol. kg(-1). min(-1) ET-1 decreased vascular compliance but had no effect on unstressed blood volume. These results show that ETs affect a variety of cardiovascular functions in trout and that branchial vascular resistance and venous compliance are especially sensitive. The multiplicity of effectors stimulated by ET suggests that this peptide was extensively integrated into cardiovascular function early on in vertebrate phylogeny.
在内未麻醉的鳟鱼中研究了内皮素(ET)-1和最近测序的同源鳟鱼ET的心血管效应,并构建了血管容量曲线以评估静脉系统对ET-1的反应性。静脉注射667 pmol/kg的ET-1可使腹主动脉压加倍;使背主动脉压(P(DA))产生三相升压-降压-升压反应;增加中心静脉压、鳃阻力和全身阻力;并降低心输出量、心率和每搏输出量。这些反应呈剂量依赖性。静脉注射鳟鱼ET(333或1000 pmol/kg)产生与ET-1基本相同的剂量依赖性心血管反应。以1和3 pmol·kg⁻¹·min⁻¹的剂量向背主动脉输注ET-1,以及以0.3和1 pmol·kg⁻¹·min⁻¹的剂量向总主静脉导管进行中心静脉输注,产生了相似的剂量依赖性心血管反应,尽管P(DA)的升高变为单相。对中心静脉输注的敏感性增加可能是由于鳃血管系统更直接地接触该肽。输注1 pmol·kg⁻¹·min⁻¹的ET-1可降低血管顺应性,但对无应激血容量无影响。这些结果表明,ETs影响鳟鱼的多种心血管功能,并且鳃血管阻力和静脉顺应性特别敏感。ET刺激的效应器的多样性表明,这种肽在脊椎动物系统发育早期就广泛整合到心血管功能中。