The effect of inhibition of prostaglandin synthesis by indomethacin on active renin and on acid-activable inactive renin was studied in nine healthy, sodium-replete men, both at rest and exercise. These volunteers were investigated after pretreatment with placebo or indomethacin, 150 mg daily for 3 days. Indomethacin induced a decrease in active (P = 0.004), total (P less than 0.001) and inactive (P = 0.02) renin at rest recumbent and at rest, sitting. Inhibition of prostaglandins with indomethacin reduced (P less than 0.001) active and total renin at each level of work load but not (P = 0.32) inactive renin. However the exercise-induced stimulation (P less than 0.05) of active and of total renin still occur during indomethacin. Indomethacin reduced (P less than 0.001) at rest, sitting and at maximal exercise the plasma concentrations of immunoreactive prostaglandins E2, prostaglandin F2 alpha and 13, 14-dihydro-15-keto-prostaglandin F alpha; the urinary excretion of immunoreactive prostaglandin E2 and F2 alpha were also reduced.
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Card Fail Rev
December 2024
Department of Medicine, University of Mississippi Medical Center Jackson, MS, US.
Aldosterone is a key regulator of fluid and electrolyte balance in the body. It is often dysregulated in heart failure (HF) and is a key driver of cardiac remodelling and worse clinical outcomes. Potassium regulation is essential for normal cardiac, gastrointestinal and neuromuscular function.
View Article and Find Full Text PDFClin Kidney J
January 2025
Department of General Internal Medicine and Nephrology, Robert Bosch Hospital Stuttgart, Stuttgart, Germany.
Background: Sparsentan, a dual-acting antagonist for both the angiotensin II receptor type 1 and the endothelin receptor type A, has emerged as a promising therapeutic agent for the treatment of IgA nephropathy (IgAN). Following the publication of the PROTECT trial, sparsentan recently received approval for the treatment of IgAN in Europe. However, it remains uncertain whether an additive effect can be observed in the context of existing treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors, given that the PROTECT study did not investigate this dual therapy approach.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
January 2025
George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah; University of Utah Spencer Fox Eccles School of Medicine.
(Pro)renin receptor (PRR) contains overlapping cleavage site for site-1 protease (S1P) and furin for generation of soluble PRR (sPRR). Although S1P-mediated cleavage mediates the release of sPRR, the functional implication of furin-mediated cleavage is unclear. Here we tested whether furin-mediated cleavage was required for the activity of sPRR in activating ENaC in cultured M-1 cells.
View Article and Find Full Text PDFHypertens Res
January 2025
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Balance between Protective vs. Exacerbating Effects of ACEIs and ARBs in Omicron Variant Infections. The spike protein on the surface of the Omicron variant has a high affinity for ACE2, making it more prone to enter cells and induce ACE2 downregulation.
View Article and Find Full Text PDFAngiotensin II (Ang II) is the most active peptide hormone produced by the renin-angiotensin system (RAS). Genetic deletion of genes that ultimately restrict Ang II formation has been shown to result in marked anemia in mice. In this study, adult mice with a genetic deletion of the RAS precursor protein angiotensinogen (Agt-KO) were used.
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