Angiotensin II and the Renal Hemodynamic Response to an Isolated Increased Renal Venous Pressure in Rats.

Xiaohua Huang,Shereen M Hamza,William A Cupples,Wenqing Zhuang,Branko Braam

doi:10.3389/fphys.2021.753355

Abstract

Elevated central venous pressure increases renal venous pressure (RVP) which can affect kidney function. We previously demonstrated that increased RVP reduces renal blood flow (RBF), glomerular filtration rate (GFR), and renal vascular conductance (RVC). We now investigate whether the RAS and RBF autoregulation are involved in the renal hemodynamic response to increased RVP. Angiotensin II (ANG II) levels were clamped by infusion of ANG II after administration of an angiotensin-converting enzyme (ACE) inhibitor in male Lewis rats. This did not prevent the decrease in ipsilateral RBF (−1.9±0.4ml/min, p<0.05) and GFR (−0.77±0.18ml/min, p<0.05) upon increased RVP; however, it prevented the reduction in RVC entirely. Systemically, the RVP-induced decline in mean arterial pressure (MAP) was more pronounced in ANG II clamped animals vs. controls (−22.4±4.1 vs. −9.9±2.3mmHg, p<0.05), whereas the decrease in heart rate (HR) was less (−5±6bpm vs. −23±4bpm, p<0.05). In animals given vasopressin to maintain a comparable MAP after ACE inhibition (ACEi), increased RVP did not impact MAP and HR. RVC also did not change (0.018±0.008ml/minˑmmHg), and the reduction of GFR was no longer significant (−0.54±0.15ml/min). Furthermore, RBF autoregulation remained intact and was reset to a lower level when RVP was increased. In conclusion, RVP-induced renal vasoconstriction is attenuated when ANG II is clamped or inhibited. The systemic effect of increased RVP, a decrease in HR related to a mild decrease in blood pressure, is attenuated also during ANG II clamp. Last, RBF autoregulation remains intact when RVP is elevated and is reduced to lower levels of RBF. This suggests that in venous congestion, the intact RBF autoregulation could be partially responsible for the vasoconstriction.

Highlights

Increased renal venous pressure (RVP) is associated with worsening of renal function in congestive states, heart failure (Damman et al, 2009; Mullens et al, 2009)
A substantial increase in RVP by 20 mmHg caused a significant reduction in renal blood flow (RBF), renal vascular conductance (RVC), and glomerular filtration rate (GFR) (Huang et al, 2018)
The RVP-induced reduction in RVC was prevented in the absence of dynamic Angiotensin II (ANG II) modulation (ANG II Clamp) and in the absence of ANG II (AVP infusion with ACE inhibition (ACEi))

Summary

Introduction

Increased renal venous pressure (RVP) is associated with worsening of renal function in congestive states, heart failure (Damman et al, 2009; Mullens et al, 2009). The RVC reduction was strongly attenuated in rats receiving a high salt diet but was unchanged after renal denervation. This suggested that the renin-angiotensin system (RAS) contributes to the renal vasoconstriction upon increased RVP. The role of the RAS in the renal hemodynamic and systemic response to RVP elevation remains unclear. Understanding this is relevant, since RAS inhibitors are frequently used in patients with heart failure and the (dis)continuation of these drugs in the context of worsening of renal function in heart failure is highly disputed

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Conclusion