Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
Department of Physiology, University of Auckland, Auckland, New Zealand.
Am J Physiol Regul Integr Comp Physiol. 2019 Sep 1;317(3):R386-R396. doi: 10.1152/ajpregu.00026.2019. Epub 2019 Jun 26.
In heart failure (HF), increases in renal sympathetic nerve activity (RSNA), renal norepinephrine spillover, and renin release cause renal vasoconstriction, which may contribute to the cardiorenal syndrome. To increase our understanding of the mechanisms causing renal vasoconstriction in HF, we investigated the interactions between the increased activity of the renal nerves and the renal release of norepinephrine and renin in an ovine pacing-induced model of HF compared with healthy sheep. In addition, we determined the level of renal angiotensin type-1 receptors and the renal vascular responsiveness to stimulation of the renal nerves and α-adrenoceptors. In conscious sheep with mild HF (ejection fraction 35%-40%), renal blood flow (276 ± 13 to 185 ± 18 mL/min) and renal vascular conductance (3.8 ± 0.2 to 3.1 ± 0.2 mL·min·mmHg) were decreased compared with healthy sheep. There were increases in the burst frequency of RSNA (27%), renal norepinephrine spillover (377%), and plasma renin activity (141%), whereas the density of renal medullary angiotensin type-1 receptors decreased. In anesthetized sheep with HF, the renal vasoconstrictor responses to electrical stimulation of the renal nerves or to phenylephrine were attenuated. Irbesartan improved the responses to nerve stimulation, but not to phenylephrine, in HF and reduced the responses in normal sheep. In summary, in HF, the increases in renal norepinephrine spillover and plasma renin activity are augmented compared with the increase in RSNA. The vasoconstrictor effect of the increased renal norepinephrine and angiotensin II is offset by reduced levels of renal angiotensin type-1 receptors and reduced renal vasoconstrictor responsiveness to α-adrenoceptor stimulation.
在心力衰竭（HF）中，肾交感神经活动（RSNA）、肾去甲肾上腺素溢出和肾素释放的增加导致肾血管收缩，这可能导致心肾综合征。为了增加我们对 HF 中肾血管收缩的机制的理解，我们研究了与健康绵羊相比，在绵羊起搏诱导的 HF 模型中，增加的肾神经活性与肾去甲肾上腺素和肾素释放之间的相互作用。此外，我们确定了肾血管紧张素 1 型受体的水平以及肾血管对肾神经和α-肾上腺素能受体刺激的反应性。在轻度 HF（射血分数 35%-40%）的清醒绵羊中，与健康绵羊相比，肾血流量（276±13 至 185±18 mL/min）和肾血管传导率（3.8±0.2 至 3.1±0.2 mL·min·mmHg）降低。RSNA 的爆发频率增加（27%），肾去甲肾上腺素溢出增加（377%），血浆肾素活性增加（141%），而肾髓质血管紧张素 1 型受体密度降低。在 HF 的麻醉绵羊中，肾神经电刺激或苯肾上腺素引起的肾血管收缩反应减弱。厄贝沙坦改善了 HF 时对神经刺激的反应，但对苯肾上腺素无反应，并降低了正常绵羊的反应。总之，在 HF 中，与 RSNA 增加相比，肾去甲肾上腺素溢出和血浆肾素活性的增加更为明显。增加的肾去甲肾上腺素和血管紧张素 II 的血管收缩作用被降低的肾血管紧张素 1 型受体水平和降低的肾血管对α-肾上腺素能受体刺激的反应性抵消。
