Renin blockade: a double-edged sword?

Aliskiren, a direct renin inhibitor, blocks the first step of the renin–angiotensin–aldosterone system (RAAS), thereby reducing plasma renin activity and the circulating levels of angiotensin I, angiotensin II, and aldosterone. Extensive RAAS blockade can be achieved through the administration of aliskiren; however, renin blockade is a double-edged sword because the renin/prorenin receptor-associated pathway is also reportedly modulated by direct renin inhibitor. This research highlight discusses the findings of a recent clinical study of aliskiren and explores the complex interactions of key molecules in the RAAS pathway in response to aliskiren administration

Renin blockade: a double-edged sword?

Aliskiren, a direct renin inhibitor, blocks the first step of the renin–angiotensin–aldosterone system (RAAS), thereby reducing plasma renin activity and the circulating levels of angiotensin I, angiotensin II, and aldosterone. Extensive RAAS blockade can be achieved through the administration of aliskiren; however, renin blockade is a double-edged sword because the renin/prorenin receptor-associated pathway is also reportedly modulated by direct renin inhibitor. This research highlight discusses the findings of a recent clinical study of aliskiren and explores the complex interactions of key molecules in the RAAS pathway in response to aliskiren administration

Elevated C-Reactive Protein Levels and Enhanced High Frequency Vasomotion in Patients with Ischemic Heart Disease during Brachial Flow-Mediated Dilation

<div><p>Purpose</p><p>The physiological role of vasomotion, rhythmic oscillations in vascular tone or diameter, and its underlying mechanisms are unknown. We investigated the characteristics of brachial artery vasomotion in patients with ischemic heart disease (IHD).</p><p>Methods</p><p>We performed a retrospective study of 37 patients with IHD. Endothelial function was assessed using flow-mediated dilation (FMD), and power spectral analysis of brachial artery diameter oscillations during FMD was performed. Frequency-domain components were calculated by integrating the power spectrums in three frequency bands (in ms²) using the MemCalc (GMS, Tokyo, Japan): very-low frequency (VLF), 0.003–0.04 Hz; low frequency (LF), 0.04–0.15 Hz; and high frequency (HF), 0.15–0.4 Hz. Total spectral power (TP) was calculated as the sum of all frequency bands, and each spectral component was normalized against TP.</p><p>Results</p><p>Data revealed that HF/TP closely correlated with FMD (r = −0.33, p = 0.04), whereas VLF/TP and LF/TP did not. We also explored the relationship between elevated C-reactive protein (CRP) levels and vasomotion. HF/TP was significantly increased in subjects with high CRP levels (CRP;>0.08 mg/dL) compared with subjects with low CRP levels (0.052±0.026 versus 0.035±0.022, p<0.05). The HF/TP value closely correlated with CRP (r = 0.24, p = 0.04), whereas the value of FMD did not (r = 0.023, p = 0.84). In addition, elevated CRP levels significantly increased the value of HF/TP after adjustment for FMD and blood pressure (β = 0.33, p<0.05).</p><p>Conclusion</p><p>The HF component of brachial artery diameter oscillation during FMD measurement correlated well with FMD and increased in the presence of elevated CRP levels in subjects with IHD.</p></div

Comparison of HRV and vasomotion in subjects with IHD.

<p>HRV; heart rate variability, IHD; ischemic heart disease, VLF; very low frequency, TP; total power, LF; low frequency; HF; high frequency.</p><p>Comparison of HRV and vasomotion in subjects with IHD.</p

Characterization of subjects with high CRP and low CRP.

<p>BP; blood pressure, eGFR; estimated glomerular filtration rate, CRP; C-reactive protein, FMD; flow-mediated dilation; HRV; heart rate variability, LF; low frequency, HF; high frequency, NS; not significant.</p><p>Characterization of subjects with high CRP and low CRP.</p

Basic characteristics of the 37 IHD subjects.

<p>IHD; ischemic heart disease, eGFR; estimated glomerular filtration rate, CRP; C-reactive protein, FMD; flow-mediated dilation; SDNN; standard deviation of normal to normal beats, HRV; heart rate variability, LF; low frequency, HF; high frequency, NS; not significant.</p><p>Basic characteristics of the 37 IHD subjects.</p

Scatter plot of the relationship between FMD or brachial artery diameter and the HF/TP power ratio of vasomotion in subjects with IHD.

<p>FMD, flow-mediated dilation; HF, high frequency; TP, total spectral power; IHD, ischemic heart disease.</p

Examples of brachial artery vasomotion of a subject with high FMD (1) and low FMD (2).

<p>HF component was enhanced in this subject with low FMD. Brachial artery diameter was continuously measured after cuff release during FMD measurement. FMD, flow-mediated dilation; DM, diabetes; VLF, very-low frequency; LF, low frequency; HF, high frequency.</p

Correlative relationship between clinical parameters and each frequency in vasomotion.

<p>VLF; very low frequency, TP; total power, LF; low frequency; HF; high frequency, Hb; hemoglonin, HbA1c; hemoglobin A1C; eGFR; estimated glomerular filtration rate, CRP; C-reactive protein, BAD; Brachial artery diameter, FMD; flow-mediated dilation; SDNN; standard deviation of normal to normal beats, NS; not significant, *; p<0.05.</p><p>Correlative relationship between clinical parameters and each frequency in vasomotion.</p

Comparison of each spectral component of vasomotion among subjects with high and low CPR level.

<p>HF, high frequency; TP, total spectral power; VLF, very low frequency; LF, low frequency; CRP, C-reactive protein.</p