Manne Krop

Learn More
The vascular effects of aliskiren last longer than expected based on its half life, and this renin inhibitor has been reported to cause a greater renin rise than other renin-angiotensin system blockers. To investigate whether aliskiren accumulation in secretory granules contributes to these phenomena, renin-synthesizing mast cells were incubated with(More)
OBJECTIVE Mannose 6-phosphate receptors (M6PR) bind both renin and prorenin, and such binding contributes to renin/prorenin clearance but not to angiotensin generation. Here, we evaluated the kinetics of renin/prorenin binding to the recently discovered human (pro)renin receptor (h(P)RR), and the idea that such binding underlies tissue angiotensin(More)
Angiotensin synthesis at tissue sites is well established, and interference with tissue angiotensin is now believed to underlie the beneficial effects of renin-angiotensin system blockers. Initially, it was thought that the renin required to synthesize angiotensin at tissue sites was also synthesized locally. However, recent studies show this is not the(More)
To study the distribution of kidney-derived renin-angiotensin system (RAS) components in humans, we monitored the decline in plasma prorenin, renin, angiotensin (Ang) I and Ang II post-nephrectomy. Prorenin and renin decreased biphasically, prorenin displaying a slower elimination. The distribution half life was similar for both. Angiotensins followed the(More)
Renin inhibitors like aliskiren not only block renin but also bind prorenin, thereby inducing a conformational change (like the change induced by acid) allowing its recognition in a renin-specific assay. Consequently, aliskiren can be used to measure prorenin. VTP-27999 is a new renin inhibitor with an aliskiren-like IC50 and t1/2, and a much higher(More)
The discovery of a (pro)renin receptor ((P)RR) in 2002 provided a long-sought explanation for tissue renin–angiotensin system (RAS) activity and a function for circulating prorenin, the inactive precursor of renin, in end-organ damage. Binding of renin and prorenin (referred to as (pro)renin) to the (P)RR increases angiotensin I formation and induces(More)
To verify the recently proposed concept that mast cell-derived renin facilitates angiotensin II-induced bronchoconstriction bronchial rings from male Sprague-Dawley rats were mounted in Mulvany myographs, and exposed to the mast cell degranulator compound 48/80 (300 microg/ml), angiotensin I, angiotensin II, bradykinin or serotonin (5-hydroxytryptamine,(More)
BACKGROUND Prorenin is an early marker of microvascular complications in diabetes. However, it can only be measured indirectly (following its conversion to renin), with a renin immunoradiometric assay (IRMA). Unfortunately, treatment with a renin inhibitor interferes with this assay, because renin inhibitors induce a conformational change in prorenin,(More)
BACKGROUND VTP-27999 is a renin inhibitor with an IC50 that is comparable to that of aliskiren, but with a higher bioavailability. Unexpectedly, VTP-27999, unlike aliskiren, did not unfold renin's precursor, prorenin, and increased the affinity of the antibodies applied in renin immunoassays. METHODS Here we verified to what degree these differences(More)
For many years, prorenin has been considered to be nothing more than the inactive precursor of renin. Yet, its elevated levels in diabetic subjects with microvascular complications and its extrarenal production at various sites in the body suggest otherwise. This review discusses the origin, regulation, and enzymatic activity of prorenin, its role during(More)