Ghrelin is a peptide hormone whose effects are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), mainly expressed in the brain but also in kidneys. The hypothesis herein raised is that GHS-R1a would be player in the renal contribution to the neurogenic hypertension pathophysiology. To investigate GHS-R1a role on renal function and hemodynamics, we used Wistar (WT) and spontaneously hypertensive rats (SHR). First, we assessed the effect of systemically injected vehicle, ghrelin, GHS-R1a antagonist PF04628935, ghrelin plus PF04628935 or GHS-R1a synthetic agonist MK-677 in WT and SHR rats housed in metabolic cages (24 h). Blood and urine samples were also analyzed. Then, we assessed the GHS-R1a contribution to the control of renal vasomotion and hemodynamics in WT and SHR. Finally, we assessed the GHS-R1a levels in brain areas, aorta, renal artery, renal cortex and medulla of WT and SHR rats using western blot. We found that ghrelin and MK-677 changed osmolarity parameters of SHR, in a GHS-R1a-dependent manner. GHS-R1a antagonism reduced the urinary Na⁺ and K⁺ and creatinine clearance in WT but not in SHR. Ghrelin reduced arterial pressure and increased renal artery conductance in SHR. GHS-R1a protein levels were decreased in the kidney and brain areas of SHR when compared to WT. Therefore, GHS-R1a role in the control of renal function and hemodynamics during neurogenic hypertension seem to be different, and this may be related to brain GHS-R1a downregulation.

Ghrelin是一种肽激素，其作用由生长激素促分泌素受体亚型1a（GHS-R1a）介导，主要在脑中和肾脏中表达。本文提出的假设是，GHS-R1a将在肾脏对神经源性高血压病理生理的贡献中发挥作用。为了研究GHS-R1a在肾功能和血液动力学中的作用，我们使用了Wistar（WT）和自发性高血压大鼠（SHR）。首先，我们评估了系统注射的媒介物生长素释放肽，GHS-R1a拮抗剂PF04628935，生长素释放肽加PF04628935或GHS-R1a合成激动剂MK-677在代谢笼中饲养的WT和SHR大鼠中的作用（24小时）。还分析了血液和尿液样本。然后，我们评估了GHS-R1a在控制WT和SHR中肾血管运动和血液动力学方面的作用。最后，我们使用蛋白质印迹法评估了WT和SHR大鼠大脑区域，主动脉，肾动脉，肾皮质和髓质中的GHS-R1a水平。我们发现ghrelin和MK-677以依赖GHS-R1a的方式改变了SHR的渗透压参数。GHS-R1a拮抗作用降低尿钠WT中有^{+ +}和K ⁺以及肌酐清除率，但SHR中没有。Ghrelin降低了SHR中的动脉压并增加了肾动脉电导率。与WT相比，SHR的肾脏和脑部GHS-R1a蛋白水平降低。因此，GHS-R1a在控制神经源性高血压期间肾功能和血流动力学中的作用似乎有所不同，这可能与脑GHS-R1a的下调有关。