Data from: The classical and alternative circulating renin-angiotensin system in normal dogs and dogs with stage B1 and B2 myxomatous mitral valve disease

The behavior of the comprehensive circulating renin‐angiotensin system (RAS) in dogs with myxomatous mitral valve disease (MMVD) before the onset of congestive heart failure remains largely unexplored. Hypothesis/Objectives: The classical and alternative RAS activity and aldosterone concentrations will be significantly higher in dogs with American College of Veterinary Internal Medicine (ACVIM) stage B2 MMVD compared to normal dogs and dogs with ACVIM stage B1 MMVD. Animals: One hundred seventeen client‐owned dogs (normal = 60; B1 = 31; B2 = 26). Methods: Prospective observational study. Angiotensin peptides (AP) and aldosterone concentrations were measured using liquid chromatography and mass spectrometry. Angiotensin converting enzymes 1 and 2 (ACE, ACE2) and renin activity surrogates were calculated from AP concentrations. Equilibrium dialysis (ED) and immediate protease inhibition (PI) methods of AP quantification were compared in 14 healthy dogs. Results: Core RAS activity and aldosterone concentrations did not differ among the 3 groups. However, the balance between the alternative and classical RAS differed, with dogs with stage B2 MMVD having significantly higher ACE2 activity surrogate (ACE2surr) when compared to normal dogs (adjusted P = .02; ratio of medians for ACE2surr [B2:normal], 1.89; 95% confidence interval [CI]: 1.4‐2.6). The ED and PI methods of AP quantification were highly correlated (AngI, r = .9, P < .0001; AngII, r = .8, P = .001). Conclusions and Clinical Importance: Circulating alternative RAS activity, specifically the surrogate measure of ACE2 activity, was increased in dogs with stage B2 MMVD as compared to normal dogs. Equilibrium dialysis results are analogous to immediate protease inhibition in dogs.

充血性心力衰竭（congestive heart failure）发作前，患有黏液瘤性二尖瓣疾病（myxomatous mitral valve disease, MMVD）的犬类体内完整循环肾素-血管紧张素系统（renin-angiotensin system, RAS）的活动特征目前仍未得到充分探索。研究假说与目的：与健康犬及美国兽医内科学会（American College of Veterinary Internal Medicine, ACVIM）B1期MMVD患犬相比，美国兽医内科学会B2期MMVD患犬的经典与非经典RAS活性及醛固酮浓度将显著升高。研究对象：117只受饲主饲养的家犬（健康组60只、B1期组31只、B2期组26只）。研究方法：本研究为前瞻性观察性研究。采用液相色谱-质谱联用法（liquid chromatography and mass spectrometry）检测血管紧张素肽（angiotensin peptides, AP）与醛固酮浓度，并基于AP浓度计算血管紧张素转换酶1、2（angiotensin converting enzymes 1 and 2, ACE、ACE2）活性及肾素活性替代指标。另纳入14只健康犬，比较平衡透析法（equilibrium dialysis, ED）与即刻蛋白酶抑制法（immediate protease inhibition, PI）两种AP定量方法的差异。研究结果：核心RAS活性与醛固酮浓度在三组间无显著差异，但非经典与经典RAS的活性平衡存在差异：B2期MMVD患犬的ACE2活性替代指标（ACE2surr）显著高于健康组（校正P=0.02；ACE2surr的中位数比值[B2:健康组]为1.89；95%置信区间[CI]：1.4~2.6）。两种AP定量方法（ED与PI）具有高度相关性（血管紧张素I[AngI]：r=0.9，P<0.0001；血管紧张素II[AngII]：r=0.8，P=0.001）。结论与临床意义：与健康犬相比，B2期MMVD患犬的循环非经典RAS活性（尤其是ACE2活性的替代检测指标）升高。平衡透析法的检测结果与即刻蛋白酶抑制法在犬体内的检测结果具有一致性。