The renin-angiotensin-aldosterone system (RAAS) is an enzymatic cascade functioning in a paracrine and autocrine fashion. In animals and humans, RAAS intrinsic to tissues modulates food intake, metabolic rate, adiposity, insulin sensitivity, and insulin secretion. A large array of observations shows that dysregulation of RAAS in the metabolic syndrome favors type 2 diabetes. Remarkably, angiote...

Aminopeptidases are key enzymes involved in the regulation of signaling peptide activity. Here, we present a detailed biochemical and structural analysis of an evolutionary highly conserved aspartyl aminopeptidase called DNPEP. We show that this peptidase can cleave multiple physiologically relevant substrates, including angiotensins, and thus may play a key role in regulating neuron function. ...

Knowledge of the structure, function and distribution of the components of the renin-angiotensin-aldosterone system (RAS) and the integrated physiological role of this hormonal system is rapidly increasing, although many questions remain unanswered. The primary structure and localisation of RAS such as renin, prorenin, angiotensinogen, angiotensin-converting enzyme (ACE) and the angiotensins ha...

Angiotensin II is a potent arterial vasoconstrictor and induces hypertension. Angiotensin II also exerts a trophic effect on cardiomyocytes in vitro. The goals of the present study were to document an in vivo increase in cardiac angiotensins in the absence of elevated plasma levels or hypertension and to investigate prevention or regression of ventricular hypertrophy by renin-angiotensin system...

The contribution of microRNA (miRNA) to the pathogenesis of renal fibrosis is not well understood. Here, we investigated whether miRNA modulates the fibrotic process in Munich Wistar Fromter (MWF) rats, which develop spontaneous progressive nephropathy. We analyzed the expression profile of miRNA in microdissected glomeruli and found that miR-324-3p was the most upregulated. In situ hybridizati...

• The cardiovascular effects of angiotensin have been studied extensively since its identification 25 years ago." The synthesis of various angiotensins and the demonstration of the pharmacological identity of the naturally occurring and the synthetic octapeptides have facilitated such studies in recent years. It has been found consistently that angiotensin is a powerful constrictor of arteriola...

We investigated in Lewis normotensive rats the effect of coronary artery ligation on the expression of cardiac angiotensin-converting enzymes (ACE and ACE 2) and angiotensin II type-1 receptors (AT1a-R) 28 days after myocardial infarction. Losartan, olmesartan, or the vehicle (isotonic saline) was administered via osmotic minipumps for 28 days after coronary artery ligation or sham operation. C...

Indirect evidence has implicated a role for central angiotensin II in blood pressure control. To answer directly the question of whether angiotensin II exists in the brain, independent of blood-borne angiotensin, and to quantify the amounts in different parts of the central nervous system, a sensitive radioimmunoassay was used to measure extracts of male adult rat brain hypothalamus and cortex ...

Intracardiac renin is considered to be involved in the pathogenesis of cardiac hypertrophy, fibrosis, and myocardial infarction. Cardiac renin is predominantly derived from the circulation, because preprorenin is not expressed locally and uptake of renin has been demonstrated. One mechanism of internalization recently described involves the mannose-6-phosphate receptor and requires glycosylatio...

It is generally acknowledged that the reninangiotensin system is of prime importance in the hierarchy of factors regulating aldosterone secretion [ 1-41. Potassium and adrenocorticotropin (ACTH) also influence aldosterone secretion [l-41 and sodium may have a direct effect on aldosterone release independent of the reninangiotensin system [2, 5, 61, at least in some species. From time to time it...