The role of renal vascular reactivity in the development of renal dysfunction during the phase of compensated and decompensated congestive heart failure

Abstract

The development of renal dysfunction plays an important role in the progression of congestive heart failure (CHF), but the exact underlying mechanism(s) remain unclear. We hypothesized that the mechanisms involved might be augmented renal vascular responsiveness to endogenous vasoconstrictors and/or impaired renal vascular responsiveness to endothelium‐dependent vasodilators. In this study we assessed renal blood flow (RBF) responses to intrarenal administration of angiotensin II (ANG II, 2 and 8 ng), norepinephrine (NE, 20 and 60 ng) and acetylcholine (Ach, 10 and 40 ng) in healthy animals and in animals with CHF during its compensated and decompensated phase.CHF was induced by volume overload achieved by creation of the aorto‐caval fistula (ACF) in normotensive Hannover Sprague‐Dawley (HanSD) rats. The animals five weeks after induction of ACF were used to represent the compensated phase of CHF and the animals 20 weeks after the induction represented the phase of decompensation. In anesthetized animals RBF was recorded by ultrasonic transit‐time flow probe (Transonic) on the renal artery. The basal RBF was significantly lower in ACF‐CHF rats, five as well as 20 weeks after ACF induction, than in sham‐operated rats (3.75 ± 0.19 and 4.65 ± 0.22 vs. 5.93 ± 0.31 ml.min−1.g−1, p<0.01 in both cases). ANG II elicited similar decreases in RBF in ACF‐CHF rats, both at five and at 20 weeks after induction of ACF when compared with sham‐operated rats (low dose: −31 ± 2 and −34 ± 3 vs. −32 ± 2% and high dose: −58 ± 2 and −61 ± 3 vs. − 57 ± 3%,). Dissimilarly, both doses of NA elicited larger decreases in RBF in ACF‐CHF rats, both at five and at 20 weeks after induction of ACF, compared with the values observed in sham‐operated rats (low dose: −31 ± 2 and −33 ± 2 vs. −20 ± 2% and high dose: −64 ± 2 and −62 ± 2 vs. 50 ± 2%, p<0.01 in both cases). Intrarenal Ach elicited greater increases in RBF in ACF‐CHF rats at five weeks after ACF induction as compared with sham‐operated rats (low dose: +59 ± 3 vs. +44 ± 2 and high dose: +69 ± 3 vs. + 53 ± 2%, p<0.05 in both cases), however, in the rats studied 20 weeks after induction of ACF, Ach‐induced increases in RBF were similar as observed in sham‐operated rats. In summary, the findings indicate that ACF‐CHF rats either in the phase of compensated or decompensated CHF do not exhibit any augmentation of renal vascular responsiveness to ANG II, but they display exaggerated renal vascular responsiveness to NE. Furthermore, the data show that during the compensation phase of CHF the rats exhibit enhanced renal vascular responsiveness to Ach, which disappears during the decompensation phase. In conclusion, our results suggest that augmented renal vascular responsiveness to ANG II and impaired renal vascular responsiveness to Ach do not play decisive role in the development of renal dysfunction in ACF‐CHF rats. On the contrary, exaggerated renal vascular responsiveness to NE may contribute to the development of renal dysfunction, both in the phase of compensated and decompensated ACF‐induced CHF.Support or Funding InformationThe study was supported by the Charles University, project GA UK No 64217 and by Ministry of Health, Czech Republic ‐ conceptual development of research organization („Institute for Clinical and Experimental Medicine – IKEM, IN 00023001”). The study was partially supported by Ministry of Health of the Czech Republic, grant nr. 15‐27735A. All rights reserved.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.