Angiotensin II Receptor Blocker, Valsartan, Increases Myocardial Blood Volume and Regresses Hypertrophy in Hypertensive Patients

Abstract

eft ventricular hypertrophy (LVH) strongly predicts cardiovascular morbidity and mortality in patients with hypertension (HT). Rates of cardiovascular events have been reported as 2-to 4-fold higher in the presence of LVH in patients with HT, independent of standard risk factors. 1,2 Moreover, regression of hypertensive LVH is associated with improved prognosis, 3,4 so prevention or reversal of LVH in patients with HT is widely accepted as a desirable treatment goal.LVH associated with HT arises from hypertrophy of cardiac myocytes and extracellular matrix collagen deposition, 5 which stiffens the left ventricular (LV) and impairs diastolic filling. Important structural remodeling processes that lead to LVH are thickening of the medial wall of the small vessels with reduced lumen diameter and lowered density of coronary capillaries, as well as accumulation of extracellular matrix collagens in the perivascular region. 6-10 Angiotensinconverting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have a regressive effect on the vascular changes in small coronary, renal, and cerebral arteries from animals with HT. 11,12 In patients with HT, a favorable effect of ACEIs and ARBs on the structure of subcutaneous small arteries has been reported. [13][14][15] However, these findings have been based on biopsies of subcutaneous tissue followed by dissection of small arteries or endomyocardial biopsies. The in vivo quantitative assessment of the myocardial microstructure thus remains to be studied in humans because of the lack of a suitable noninvasive technique.Recently, Vogel et al demonstrated that myocardial contrast echocardiography (MCE) could accurately measure the myocardial microvascular parameters, relative myocardial blood volume (MBV) and its exchange frequency (β). 16 Moreover, we have also reported a quantitative method of measuring MBV by harmonic power Doppler imaging during MCE, which can overcome the acoustic field inhomogeneity and correctly measure MBV in the diseased heart. 17 The MBV corresponds to the intravascular volume fraction and thus reflects the lumen diameter and density of capillaries, as well as perivascular fibrotic changes, within the region of interest (ROI). By using this technique, Indermuhle et al found that MBV was decreased in patients with HT. 18 However, it remains to be examined whether this decrease in MBV can be reversed by antihypertensive Sanae Kaga, BA**; Mutsumi Nishida, PhD**; Chikara Shimizu, MD**; Kazuhiko Matsuno, MD**; Hiroyuki Tsutsui, MD Background: Although a reduction in myocardial blood volume (MBV), an in vivo index of the myocardial microvasculature, measured by myocardial contrast echocardiography in patients with hypertension (HT), can be demonstrated, it is still unknown whether a decreased MBV can be improved by antihypertensive treatment. Methods and Results: Eleven HT patients (mean age 58 years, 7 men) with left ventricular hypertrophy (LVH) and 10 age-and sex-matched normal controls were studied. Harmonic power Doppler images were acqu...

Retraction:Enhanced Cardiovascular Protective Effects of Valsartan in High-Risk Hypertensive Patients With Left Ventricular Hypertrophy

“…27 Another recent report has also shown that mean blood volume measured on myocardial contrast echocardiography, an indicator of the myocardial microvascular narrowing, is decreased in hypertensive patients with LVH, and valsartan corrects the decreased mean blood volume in those patients. 28 These facts might therefore account for the enhanced reduction of cardiovascular events, particularly angina pectoris, by valsartan in hypertensive patients with LVH.…”

Spontaneous Development of Left Ventricular Hypertrophy and Diastolic Dysfunction in Mice Lacking All Nitric Oxide Synthases

“…We previously revealed that the renin-angiotensin system, as evaluated by the tissue levels of angiotensin-converting enzyme and AT1 receptor and the plasma levels of renin and angiotensin II, was activated in the n/i/eNOS -/-mice. 10, 33 The renin-angiotensin system plays an important role in the pathogenesis of heart diseases. 34, 35 Based on the evidence, we further tested our hypothesis that the AT1 receptor signal transduction pathway mediates cardiac abnormalities in the n/i/eNOS -/-mice.…”

Impact of Left Ventricular Hypertrophy on the Time-Course of Renal Function in Hypertensive Patients - A Subanalysis of the CASE-J Trial -

“…22 In the heart, LVH might be analogous to renal damage because longstanding exposure to high BP leads to LVH. 23 We previously reported that LVH was strongly associated with the risk of cerebrovascular events (adjusted HR: 2.38; 95%CI: 1.62-3.48; P<0.001). 10 Furthermore, higher urinary albumin excretion has been observed in patients with LVH, 24,25 suggesting that cardiac and glomerular vascular damage might occur concurrently.…”