Structure and Regulation of Prorenin

The treatment and prevention of cardiovascular disease is one ofthe triumphs of modern medicine but we have a long way to go before this success is completed. Heart attack and stroke are still common and, in the western world, cardiovascular disease remains the main cause of morbidity and mortality. A major player in cardiovascular homeostasis is the renin.angiotensin system (RAS), and the growing knowledge of this system has led to the development of agents that specifically interact with components that are part of the RAS. 'Anti-RAS' drugs are now widely used in the management of hypertension, heart failure and diabetic nephropathy. However, as is true for cardiovascular medicine in general, many problems remain to be solved. Our understanding of how the RAS works and how to modify its actions is still far from complete. One century ago Tigerstedt and Bergmann coined the name 'renin' for a hypertensive factor in rabbit kidney. I They showed that this factor was present in renal cortex and that it was secreted into renal venous blood. It was retained by dialysis membranes and sensitive to heat, which suggested its protein. nature. After these initial observations renin sank into oblivion for a few decades until interest flared up after the experiments by Goldblatt et al., who showed that clamping a renal artery in a dog caused hypertension. They believed a humoral factor to be the hypertensive principle, which was shown to be renin by Pickering et al. From then on unraveling of the structure of what nowadays is known as the RAS made steady progress, culminating in the cloning of the genes of its constituents

Improved immunoradiometric assay for plasma renin

BACKGROUND: Our renin IRMA overestimated renin in plasmas with high prorenin-to-renin ratios. We suspected that the overestimation of renin was caused less by cross-reactivity of the renin-specific antibody with prorenin than by a conformational change of prorenin into an enzymatically active form during the assay. METHODS: Because the inactive form of prorenin converts slowly into an active form at low temperature, we raised the assay temperature from 22 degrees C to 37 degrees C, simultaneously shortening the incubation time from 24 to 6 h. The former IRMA was performed in <1 working day with these modifications. RESULTS: The comeasurement of prorenin as renin was eliminated. Reagents were stable at 37 degrees C, and the new and old IRMAs were comparable in terms of precision and accuracy. The functional lower limit of the assay (4 mU/L) was below the lower reference limit (9 mU/L). The modified IRMA agreed closely with the activities measured with an enzyme-kinetic assay. Results were not influenced by the plasma concentration of angiotensinogen. At normal angiotensinogen concentrations, the IRMA closely correlated with the classical enzyme-kinetic assay of plasma renin activity. CONCLUSION: The modified IRMA, performed at 37 degrees C, avoids interference by prorenin while retaining the desirable analytical characteristics of the older IRMA and requiring less time

Shrinkage of the distal renal artery 1 year after stent placement as evidenced with serial intravascular ultrasound

The objective of this study was to determine the quantitative intravascular ultrasound (IVUS) and angiographic changes that occur during 1 year follow-up after renal artery stent placement, given that restenosis continues to be a limitation of renal artery stent placement. 38 consecutive patients with symptomatic renal artery stenosis treated with Palmaz stent placement were studied prospectively. IVUS and angiography were performed at the time of stent placement and at 1 year follow-up. At follow-up, angiographic restenosis was seen in 14% of patients. The lumen area in the stent, seen with IVUS, was significantly decreased from 24+/-5.6 mm(2) to 17+/-5.6 mm(2) (p<0.001) solely due to plaque accumulation. The distal main renal artery showed a significant decrease in lumen area owing to a significant vessel area decrease from 39+/-14.0 mm(2) to 29+/-9.3 mm(2) (p<0.001) without plaque accumulation. Angiographic analysis confirmed this reduction in luminal diameter and showed that the distal renal artery diameter at follow-up was significantly smaller than before stent placement (86+/-23.0% vs 104+/-23.9% of the contralateral renal artery diameter; p=0.003). Besides plaque accumulation in the stent, unexplained shrinkage of the distal main renal artery was evidenced with IVUS and angiography 1 year following stent placement