Involvement of (pro)renin receptor in the glomerular filtration barrier

(Pro)renin receptor-bound prorenin not only causes the generation of angiotensin II via the nonproteolytic activation of prorenin, it also activates the receptor’s own intracellular signaling pathways independent of the generated angiotensin II. Within the kidneys, the (pro)renin receptor is not only present in the glomerular mesangium, it is also abundant in podocytes, which play an important role in the maintenance of the glomerular filtration barrier. Recent in vivo studies have demonstrated that the overexpression of the (pro)renin receptor to a degree similar to that observed in hypertensive rat kidneys leads to slowly progressive nephropathy with proteinuria. In addition, the handle region peptide, which acts as a decoy peptide and competitively inhibits the binding of prorenin to the receptor, is more beneficial than an angiotensin-converting enzyme inhibitor with regard to alleviating proteinuria and glomerulosclerosis in experimental animal models of diabetes and essential hypertension. Thus, the (pro)renin receptor may be upregulated in podocytes under hypertensive conditions and may contribute to the breakdown of the glomerular filtration barrier

Blood pressure-independent effect of candesartan on cardio-ankle vascular index in hypertensive patients with metabolic syndrome

Kanako Bokuda1, Atsuhiro Ichihara1,2, Mariyo Sakoda1, Asako Mito1, Kenichiro Kinouchi1, Hiroshi Itoh11Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Endocrinology and Anti-Aging Medicine, Keio University School of Medicine, Tokyo, JapanAbstract: Angiotensin receptor blockers (ARBs) are known to reduce the cardiovascular risk in hypertensive patients. This study was designed to examine the effect of an ARB candesartan on subclinical atherosclerosis assessed by cardio-ankle vascular index (CAVI) in comparison with calcium channel blockers (CCBs) alone in hypertensive patients with metabolic syndrome (MetS). A total of 53 consecutive hypertensive patients with MetS were randomly assigned to the candesartan group, in which candesartan was added on, or the CCBs group, in which CCBs were added on. Clinical and biological parameters were obtained before and after the 12-month treatment period. The primary measure of efficacy was the %change in CAVI. When treated with candesartan, but not CCBs, CAVI significantly decreased from 8.7 to 7.7 by 11%. Blood pressure (BP) significantly decreased with both treatments, but the differences between groups were not significant. The changes in other parameters remained unchanged in both the groups. Analysis of covariance found that both the BP reduction and the therapy difference contributed to the decrease in CAVI, but the BP reduction was not involved in the decrease in CAVI caused by the difference in the therapy. Candesartan may be a better antihypertensive drug than CCBs to that subclinical atherosclerosis of patients with MetS.Keywords: albuminuria, ambulatory blood pressure, calcium channel blockers, carotid ­intima-media thicknes

Cilnidipine and Telmisartan Similarly Improves Vascular Damage in Hypertensive Patients

This study was designed to compare the effects of 12-month blood pressure (BP) control using cilnidipine and telmisartan on vascular damage in untreated hypertensive patients. One hundred patients were randomly assigned to either a cilnidipine group or a telmisartan group. The extent of vascular damage was assessed before and after treatment by measuring urinary albumin excretion (UAE), pulse wave velocity (PWV), and intima-media thickness (IMT) of the carotid arteries in each patient. Both drugs similarly decreased BP without altering plasma markers for oxidative stress or inflammation. Both UAE and PWV were significantly improved in both groups, but IMT was significantly reduced only in the cilnidipine group. Multiple regression analyses suggested that the UAE may have decreased as a result of a reduction in intraglomerular pressure caused by telmisartan or by efferent arteriolar dilation caused by cilnidipine. In addition, the PWV may have decreased as a result of the improvement in lipid metabolism caused by telmisartan or the reduction in plasma levels of aldosterone caused by cilnidipine. However, the analyses could not identify any definitive causal relationships or suggest the mechanism responsible for the improvement in IMT caused by cilnidipine. Thus, telmisartan and cilnidipine have unique properties for inhibiting vascular complications

Prorenin Receptor Is Essential for Normal Podocyte Structure and Function

The prorenin receptor is an accessory subunit of the vacuolar H(+)-ATPase, suggesting that it has fundamental functions beyond activation of the local renin-angiotensin system. Podocytes express the prorenin receptor, but its function in these cells is unknown. Here, podocyte-specific, conditional, prorenin receptor-knockout mice died of kidney failure and severe proteinuria within 4 weeks of birth. The podocytes of these mice exhibited foot process effacement with reduced and altered localization of the slit-diaphragm proteins nephrin and podocin. Furthermore, the podocytes contained numerous autophagic vacuoles, confirmed by enhanced accumulation of microtubule-associated protein 1 light chain 3-positive intracellular vesicles. Ablation of the prorenin receptor selectively suppressed expression of the V(0) c-subunit of the vacuolar H(+)-ATPase in podocytes, resulting in deacidification of intracellular vesicles. In conclusion, the prorenin receptor is important for the maintenance of normal podocyte structure and function