In the treatment of patients with hypertension and renal-artery stenosis, angioplasty has little advantage over antihypertensive-drug therapy.

Aside from a well-documented induction of angiotensinogen, ERT is related to a substantial suppression of renin, a phenomenon that might have received little attention because of widely used indirect measurements of the hormone.

The existence of a cardiac renin-angiotensin system, independent of the circulating renin-angiotensin system, is still controversial. We compared the tissue levels of reninangiotensin system components in the heart with the levels in blood plasma in healthy pigs and 30 hours after nephrectomy. Angiotensin I (Ang I)-generating activity of cardiac tissue was identified as renin by its inhibition with a specific active site-directed renin inhibitor. We took precautions to prevent the ex vivo generation and breakdown of cardiac angiotensins and made appropriate corrections for any losses of intact Ang I and II during extraction and assay. Tissue levels of renin (n=ll) and Ang I (n=7) and II (n=7) in the left and right atria were higher than in the corresponding ventricles (P< .05). Cardiac renin and Ang I levels (expressed per gram wet weight) were similar to the plasma levels, and Ang II in cardiac tissue was higher than in plasma (P<.05). The presence of these renin-angiotensin system components in cardiac tissue therefore cannot be accounted for by trapped plasma or simple diffusion from plasma into the interstitial fluid. Angiotensinogen levels (n=ll) in cardiac tissue were 10% to 25% of the A ngiotensin I (Ang I) is produced in the circulating / \ blood by the action of renin from the kidney on -Z A . angiotensinogen produced by the liver. Ang I is converted to Ang II, a potent vasoconstrictor, by angiotensin-converting enzyme (ACE) located on the luminal surface of the vascular endothelium. It is now well established that Ang I and II are not only produced in the blood compartment but also locally in tissues. Recent evidence suggests that complete local reninangiotensin systems (RAS) are present in a number of organs, for instance, kidney, adrenal gland, and ovary. 13In such local RAS, the production of Ang I and II is thought to depend on in situ synthesized renin rather than plasma-derived renin.A local cardiac RAS has also been postulated. 4 ' 5 However, direct evidence for Ang I and II production in the heart by in situ synthesized renin is still lacking. Renin mRNA levels in the heart are usually low and can be detected only by polymerase chain reaction. 68 Early studies showed Ang I-generating activity in left ventric-

Renin, prorenin, and immunoreactive renin were present in vitreous and subretinal fluid of eyes from subjects with and without diabetic retinopathy. Renin substrate, albumin, transferrin, and immunoglobin G were also found in these ocular fluids. In many samples renin levels were close to the detection limit of the assay. The levels of renin substrate, albumin, transferrin, and immunoglobulin G varied widely among ocular fluid samples, but in each individual sample the levels were, relative to each other, similar to those in plasma. In contrast, the prorenin level in ocular fluid was up to 100 times higher than expected on the basis of the plasma protein content of ocular fluid. Moreover, there was little difference in prorenin concentrations between samples with low and high plasma protein contents. Prorenin, relative to albumin and other plasma proteins, was higher in vitreous fluid from eyes with proliferative diabetic retinopathy complicated by traction retinal detachment than in eyes of nondiabetic subjects with spontaneous retinal detachment. It appears that prorenin (and possibly renin) in ocular fluid is controlled by an active and specific process, possibly local synthesis within the eye. In view of the vascular actions of angiotensin II, an intraocular renin-angiotensin system may play a role in diabetic retinopathy.

These data demonstrate that there is a sexual dimorphism of prorenin levels in humans, suggesting that sex hormones affect the regulation of the renin gene. Data confirm previous reports of elevated prorenin levels in diabetics and older subjects, as well as of lower than normal prorenin levels in subjects with hypertension in smaller populations. Our findings may help to clarify the potential (patho)physiologic functions of prorenin and to identify the factors that influence the constitutive secretion and intracellular processing of this prohormone.

No abstract

These data in patients with heart failure support the concept of local angiotensin production in the heart by renin that is taken up from the circulation. Membrane binding may be part of the uptake process.

Progression of microalbuminuria (defined as urinary albumin excretion rate (AER) of 30±300 mg/24h [1]) to overt diabetic nephropathy in patients with Type I (insulin-dependent) diabetes mellitus is retarded by treatment with inhibitors of angiotensin converting enzyme (ACE). Even at the microalbuminuric stage, pathologic changes are present in the kidney [2] together with widespread endothelial dysfunction [3] [4]. Microalbuminuria is associated with excess cardiac morbidity [5]. It may therefore be worthwile to identify diabetic patients at risk before the stage of microalbuminuria, to start preventive treatment. Several risk factors for progression to microalbuminuria have been proposed [6,7], such as poor metabolic control, hypertension and high-normal AER.The most attractive factors for identifying risk are those involved in the pathogenesis of the disease. The favourable response to ACE inhibitors [8,9] suggests that the renin angiotensin system is one which is supported by experimental evidence that angiotensin II (AngII) is an important factor in the pathogenesis Diabetologia (1999) Abstract Aims/hypothesis. The renin-angiotensin system is possibly involved in the pathogenesis of diabetic nephropathy. The most striking change in renin-angiotensin system components in blood of patients with diabetic nephropathy is an increased prorenin concentration. We investigated prospectively serum concentrations of renin-angiotensin system components and the time course of prorenin increase in normoalbuminuric diabetic patients developing microalbuminuria. Methods. Patients (n = 199) with Type I (insulin-dependent) diabetes mellitus and normoalbuminuria at baseline were prospectively followed for 10 years. The prorenin concentrations and other variables possibly associated with the occurrence of microalbuminuria, were investigated by Cox-regression analysis. Results. Of the patients 29 developed microalbuminuria. Glycated haemoglobin values were higher at baseline in these patients. Serum prorenin was similar at baseline but rose in the 29 patients before the development of microalbuminuria and was stable in patients with stable albumin excretion. Renin, angiotensinogen and angiotensin converting enzyme serum concentrations were stable in both groups. Prorenin and glycated haemoglobin were independent prognostic factors for the development of microalbuminuria. A prognostic index, based on these variables, was constructed to estimate the relative risk of developing microalbuminuria. Conclusions/interpretation. Increase in serum prorenin precedes onset of microalbuminuria in normotensive patients with insulin-dependent diabetes mellitus. High concentrations of prorenin in combination with high values of glycated haemoglobin can be used as a predictor of development of microalbuminuria. [Diabetologia (1999