Mesh : Rats Animals Receptors, Dopamine D3 Desoxycorticosterone Acetate / pharmacology Endothelin Receptor Antagonists / pharmacology Rats, Inbred SHR Hypertension / chemically induced Endothelins / pharmacology Water Acetates / pharmacology Blood Pressure Endothelin-1

来  源:   DOI:10.26402/jpp.2024.1.02

Abstract:
Endothelins and renal dopamine contribute to control of renal function and arterial pressure in health and various forms of experimental hypertension, the action is mediated by tonic activity of specific receptors. We determined the action mediated by endothelin type B and by dopamine D3 receptors (ETB-R, D3-R) in anaesthetized spontaneously hypertensive (SHR) and in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In rats of both hypertension models infused during 60 min into the interstitium of in situ kidney were either ETB-R antagonist, BQ788 (0.67 mg kg-1 BW h-1) or D3-R antagonist, GR103691 (0.2 mg kg-1 BW h-1). Arterial pressure (MAP), renal artery blood flow (RBF, transonic probe) and renal medullary blood flow (MBF, laser-Doppler) were measured along with sodium, water and total solute excretion (UNaV, V, UosmV). Experiments with ETB-R blockade confirmed their tonic vasodilator action in the whole kidney (RBF) and medulla (MBF) in both hypertension models. In SHR only, the first evidence was provided that ETB-R specifically increases transtubular backflux of non-electrolyte solutes. In DOCA-salt rats ETB-R blockade caused an early decrease in water and salt transport whereas an increase was often reported from many previous studies. The most striking effect of D3-R blockade in SHR was a selective increase in MBF, which strongly suggested tonic vasoconstrictor action of these receptors in the renal medulla; this speaks against prevailing opinion that D3 receptors are virtually inactive in SHR. In our model variant of DOCA-salt rats of D3-R blockade clearly caused a rapid major increase in MAP in parallel with depression of renal haemodynamics.
摘要:
内皮素和肾脏多巴胺有助于控制健康和各种形式的实验性高血压的肾功能和动脉压,该作用是由特定受体的补品活性介导的。我们确定了内皮素B型和多巴胺D3受体介导的作用(ETB-R,D3-R)在麻醉的自发性高血压(SHR)和醋酸脱氧皮质酮(DOCA)盐高血压大鼠中。在两种高血压模型的大鼠中,在60分钟内输注到原位肾脏间质中的任一种是ETB-R拮抗剂,BQ788(0.67mgkg-1BWh-1)或D3-R拮抗剂,GR103691(0.2mgkg-1BWh-1)。动脉压(MAP),肾动脉血流量(RBF,跨音速探针)和肾髓质血流(MBF,激光多普勒)与钠一起测量,水和总溶质排泄(UNAV,V,UosmV)。在两种高血压模型中,ETB-R阻断的实验证实了它们在整个肾脏(RBF)和延髓(MBF)中的强直血管舒张作用。仅在SHR中,第一个证据是ETB-R特异性增加非电解质溶质的经管反流.在DOCA盐大鼠中,ETB-R阻断导致水和盐运输的早期减少,而许多先前的研究经常报道这种增加。D3-R阻断在SHR中最显著的作用是选择性增加MBF,这强烈暗示了这些受体在肾髓质中的强直血管收缩作用;这与普遍的观点相反,即D3受体在SHR中实际上是无活性的。在我们的D3-R阻断的DOCA盐大鼠模型变体中,明显引起MAP的快速大幅增加,同时抑制了肾脏血流动力学。
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