Short-Lived Active Prorenin: Precursor of So-Called Native Prorenin.

The enzymatic activity of the aspartic protease, renin, is critical for its function in blood pressure regulation and sodium homeostasis. Incubation of so-called native prorenin at low pH leads to its activation. After binding to transition-state mimicking renin inhibitors at neutral pH, prorenin attains the active conformation, as indicated by immunosorbent assay using monoclonal antibodies specific for epitopes of the prosegment or the renin body.

New renin inhibitor VTP-27999 alters renin immunoreactivity and does not unfold prorenin.

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 bioavailability.

How does the angiotensin II type 1 receptor 'trump' the type 2 receptor in blood pressure control?

Background: A kinetic model for the binding of angiotensin II (Ang II) to AT1 receptors (AT1Rs) in arterioles did suggest a novel mechanism of association rate amplification and facilitated Ang II diffusion in vivo.

Aim Of Study: To examine how this mechanism, acting on AT1R, will affect the stimulation of AT2R.

Method: The model distinguishes between the diffusion of plasma Ang II across the endothelium layer (thickness 10(-4) - 5 × 10(-4) cm) into the vascular smooth muscle (VSM) layer (5 × 10(-4) cm), and the diffusion of tissue Ang II from perivascular interstitium (thickness of micromilieu fluid layer at abluminal VSM surface 10(-6) - 10(-5) cm, i.

Facilitated diffusion of angiotensin II from perivascular interstitium to AT1 receptors of the arteriole. A regulating step in vasoconstriction.

Background: A kinetic model for the binding of angiotensin (Ang) II to AT1 receptors (AT1R) in arterioles in vivo did suggest a novel mechanism of stimulus amplification.

Objective: To further clarify the role of this mechanism in the functioning of the local renin-angiotensin systems, as opposed to circulating Ang II.

Methods And Results: The model was refined in order to account for geometric characteristics of the vascular smooth muscle (VSM) cells in arterioles with a single VSM cell layer.