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. 2024 Jun 3;25(11):6169.
doi: 10.3390/ijms25116169.

Study on the Effects of Angiotensin Receptor/Neprilysin Inhibitors on Renal Haemodynamics in Healthy Dogs

Mio Ishizaka  1 , Yurika Yamamori  1 , Huai-Hsun Hsu  1 , Yuichi Miyagawa  1 , Naoyuki Takemura  1 , Mizuki Ogawa-Yasumura  1
Affiliations

Study on the Effects of Angiotensin Receptor/Neprilysin Inhibitors on Renal Haemodynamics in Healthy Dogs

Mio Ishizaka et al. Int J Mol Sci. .

Abstract

An angiotensin receptor/neprilysin inhibitor (ARNI), a heart failure treatment, is a combination drug made up of sacubitril, a neprilysin inhibitor, and valsartan, a vascular receptor blocker. No human or veterinary studies regarding the effect of ARNI on renal haemodynamics in the absence of cardiac or renal issues exist. Therefore, we investigated the effect of ARNI on renal haemodynamics in five healthy dogs. ARNI was administered to all five dogs at an oral dose of 20 mg/kg twice daily for 4 weeks. Renal haemodynamics were assessed on the day before ARNI administration (BL), on Day 7, and on Day 28. The glomerular filtration rate (GFR) significantly increased on Day 28 compared to BL and Day 7, whereas renal plasma flow increased on Day 7 and Day 28 compared to BL. Systolic blood pressure significantly decreased between BL and Day 28. Plasma atrial natriuretic peptide (ANP) concentrations increased on Day 7 compared to BL. Additionally, ANP concentrations increased on Day 28 in three of the five dogs. Different ANP concentrations were observed in the remaining two dogs. Both urine output volume and heart rate remained relatively stable and did not exhibit significant change. In conclusion, ARNI may enhance renal haemodynamics in healthy dogs. ARNI could be a valuable drug for treating both heart and kidney disease in dogs.

Keywords: angiotensin receptor/neprilysin inhibitor; glomerular filtration rate; renal haemodynamics; renal plasma flow.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Scatter diagram comparing the CCr for BL, Day 7, and Day 28. In the plot, the centre line represents the median. * p < 0.05.
Figure 2
Figure 2
Scatter diagram comparing the CPAH on BL, Day 7, and Day 28. In the plot, the centre line represents the median.
Figure 3
Figure 3
Scatter diagram comparing systolic blood pressure on BL, Day 7, and Day 28. In the plot, the centre line represents the median. * p < 0.05.
Figure 4
Figure 4
Scatter diagram comparing plasma ANP concentrations on BL, Day 7, and Day 28. In the plot, the centre line represents the median.
Figure 5
Figure 5
Scatter diagram comparing urine output on BL, Day 7, and Day 28. In the plot, the centre line shows the median.
Figure 6
Figure 6
Scatter diagram comparing heart rate on BL, Day 7, and Day 28. In the plot, the centre line shows the median.
Figure 7
Figure 7
Experimental procedure. We performed this process on the day before administration (BL), Day 7, and Day 28. CRI, continuous rate infusions; black arrowhead, the timing of complete urination and urine sampling; white arrowhead, the timing of blood sampling.
See this image and copyright information in PMC

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This study received no external funding.

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