Protein Kinase G Is Involved in Acute but Not in Long-Term Regulation of Renin Secretion

Frontiers in Pharmacology
Andrea SchrammJens Schlossmann

Abstract

Pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) is, in combination with diuretics, the first-choice treatment for hypertension, although 10-20% of patients do not respond adequately. Next to the RAAS, the nitric oxide/cGMP/protein kinase G (PKG) system is the second fundamental blood pressure regulator. Whether both systems influence each other is not well-studied. It has been shown that nitric oxide (NO) supports renin recruitment via activation of soluble guanylate cyclase (sGC) and subsequent generation of cGMP. Whether this leads to an ensuing activation of PKGs in this context is not known. PKGIα, as well as PKGII, is expressed in renin-producing cells. Hence, we analyzed whether these enzymes play a role regarding renin synthesis, secretion, or recruitment. We generated renin-cell-specific PKGI-knockout mice and either stimulated or inhibited the renin system in these mice by salt diets. To exclude the possibility that one kinase isoform can compensate the lack of the other, we also studied double-knockout animals with a conditional knockout of PKGI in juxtaglomerular cells (JG cells) and a ubiquitous knockout of PKGII. We analyzed blood pressure, renin mRNA and renal renin protein content as...Continue Reading

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Citations

Nov 21, 2019·Biological Chemistry·Franz Hofmann
Jun 3, 2021·International Journal of Molecular Sciences·Michael MajerJens Schlossmann
Aug 7, 2021·Journal of Cardiovascular Development and Disease·Nasim KiaieAmirhossein Sahebkar

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Methods Mentioned

BETA
glycosylation
PCR
biopsies
enzyme-linked immunosorbent assay
ELISA

Software Mentioned

axiovision
ImageLab
GraphPad Prism

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