The intrarenal renin-angiotensin system: does it exist? Implications from a recent study in renal angiotensin-converting enzyme knockout mice.

A large body of evidence supports the presence of local production of angiotensins in the kidney. It is widely believed that renin-angiotensin system (RAS) blockers, through interference with such production and/or the local effects of angiotensin (Ang) II, exert protective renal effects. Yet, whether such production affects blood pressure independently from the circulating RAS is still a matter of debate.

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors.

The renin-angiotensin system (RAS) has a vital role in regulating the cardiovascular system. The primary effector of the RAS is the octapeptide angiotensin (Ang) II, a potent regulator of blood pressure and water homeostasis. Ang II mediates its functions through the stimulation of two distinct receptors, AT(1) (two subtypes in rodents (AT(1a) and AT(1b))) and AT(2).

Evaluation of a direct prorenin assay making use of a monoclonal antibody directed against residues 32-39 of the prosegment.

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, thereby allowing its detection as renin.

Angiotensin II induces phosphorylation of the thiazide-sensitive sodium chloride cotransporter independent of aldosterone.

We studied here the independent roles of angiotensin II and aldosterone in regulating the sodium chloride cotransporter (NCC) of the distal convoluted tubule. We adrenalectomized three experimental and one control group of rats. Following surgery, the experimental groups were treated with either a high physiological dose of aldosterone, a non-pressor, or a pressor dose of angiotensin II for 8 days.

Osmomediated natriuresis in humans: the role of vasopressin and tubular calcium sensing.

Background: The aim was to investigate the unknown mechanism of osmomediated natriuresis. This is the phenomenon by which hypertonic saline (HS) produces a larger natriuresis than isotonic saline (IS), despite the same sodium content.

Methods: Seven healthy volunteers first received HS and then IS (both 3.

The risk of myocardial infarction in patients with reduced activity of cytochrome P450 2C9.

Objective: The aim of the present follow-up study was to investigate whether the enzyme activity of the human cytochrome P450 (CYP) 2C9 isoenzyme is associated with myocardial infarction.

Methods: We investigated whether the variant alleles CYP2C9*2 and CYP2C9*3 or the use of CYP2C9 substrates or inhibitors was associated with an increased risk of myocardial infarction in 2210 men and 3534 women from the Rotterdam Study, a prospective population-based cohort study of individuals aged 55 years or older.

Results: In women, the use of CYP2C9 substrates or inhibitors was significantly associated with incident myocardial infarction with a hazard ratio of 2.