Tonic action of endothelin type B and dopamine D3 receptors in SHR and DOCA hypertensive rats: effects of intrarenally applied selective antagonists

Abstract

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 dopamine D3 receptors (ETB-R, D3-R) in anesthetized spontaneously hypertensive (SHR) and in 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 h-1) or D3-R antagonist, GR169031 (0.2 mg kg-1 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, such as urea. 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 D3-R blockade clearly caused a rapid major increase in MAP in parallel with depression of renal haemodynamics