Role of cGMP-kinase II in the control of renin secretion and renin expression.

Wagner, Charlotte; Pfeifer, Alexander; Ruth, Peter; Hofmann, Franz; Kurtz, Armin

doi:10.1172/jci4044

Cited by 82 publications

(57 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cyclic GMP has been shown to inhibit renin expression and secretion. 40 Activation of cGMPdependent protein kinases by cGMP decreased renin secretion from the isolated perfused rat kidney, isolated renal juxtaglomerular cells, and kidney slices. 40 -42 PGE2 enhances renin production 43 through stimulation of EP3 and EP4 receptors.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin Subtype-2 Receptors Inhibit Renin Biosynthesis and Angiotensin II Formation

et al. 2005

View full text Add to dashboard Cite

Abstract-Renin is regulated by angiotensin subtype 1 (AT 1 ) receptor, but it is unknown whether angiotensin subtype 2 (AT 2 ) receptor contributes to this regulation. We hypothesized that AT 2 receptors inhibit angiotensin II (Ang II) through inhibition of renin biosynthesis. We monitored changes in renal Ang II, renin mRNA and protein expression, and plasma renin concentration (PRC) in response to renal cortical administration of the AT 1 receptor blocker valsartan or the AT 2 receptor blocker PD 123319 (PD) in conscious rats administered low sodium intake (LS (Ang II) is the major effector hormone of the renin-angiotensin system (RAS). Most of the known physiological functions and pathologic effects associated with Ang II are mediated by the angiotensin subtype 1 (AT 1 ) receptor, including renin inhibition. 1 In contrast, the functions of the angiotensin subtype 2 (AT 2 ) receptor are still being elucidated. The AT 2 receptor is expressed abundantly during fetal development and declines after birth. [1][2][3] In mammalian adults, the AT 2 receptor had been reported in multiple organs, including the kidney. 4 -6 Currently, the AT 2 receptor has several described functions related to inhibition of cell growth, promotion of cell differentiation, and stimulation of apoptosis. [7][8][9][10][11][12] Previously, we demonstrated that during sodium depletion, the AT 2 receptor mediates renal production of bradykinin, nitric oxide (NO), and cGMP. [13][14][15][16][17] Unlike the well-known effect of AT 1 receptor on renin production, 18 -19 the influence of the AT 2 receptor on renal renin biosynthesis and Ang II production is not known.In this study, we tested the hypothesis that the AT 2 receptor inhibits renal renin synthesis and Ang II production. We used multiple techniques including renal interstitial microdialysis, [13][14][15][16][17] real-time quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, and enzymelinked immunoassays for monitoring changes in renal Ang II, renin mRNA, renin protein expression, and plasma renin concentration to investigate whether intrarenal AT 2 receptors regulate renin production and Ang II formation. We monitored renal interstitial levels of Ang II in conscious rats during sodium restriction, a condition known to increase AT 2 receptor expression, and during AT 1 and AT 2 receptor blockade. 5 A distinct advantage of the microdialysis technique 13 is the ability to monitor renal Ang II levels in conscious rats without undesirable hemodynamic changes. In this study, we demonstrate for the first time to our knowledge that AT 2 receptors regulate the activity of the RAS through inhibition of renin biosynthesis in young rats. Methods Renal Microdialysis TechniqueFor the determination of renal interstitial fluid (RIF) Ang II, we constructed a microdialysis probe as previously described. [13][14][15][16][17] In vitro, best recovery for Ang II was observed with a perfusion rate of 3 L/min, and was Ϸ53%. Animal PreparationThe experiments were approved by the U...

show abstract

Section: Discussionmentioning

confidence: 99%

Angiotensin Subtype-2 Receptors Inhibit Renin Biosynthesis and Angiotensin II Formation

et al. 2005

View full text Add to dashboard Cite

show abstract

“…4 Center and Right). PKGI is not expressed in renal parenchyma (11,12), but PKGII inhibits renin secretion and adrenal aldosterone production (13). However, the level of renal expression of PKGII in LZM and WT kidneys was identical (Fig.…”

Section: Studies (Si Text)mentioning

confidence: 93%

“…PKGI is expressed in vascular and all smooth muscle cells, as well as platelets, the central nervous system, and renal mesangial and interstitial myofibroblasts, but not in renal parenchymal cells (11,12), whereas PKGII is expressed in the brain, intestinal mucosa, chondrocytes, lung, renal parenchyma, and the renal reninsecreting cells and adrenal zona glomerulosa cells. PKGII but not PKGI inhibits renin secretion by the kidney (13,14) and regulates basal aldosterone production by the adrenal gland (15). PKGI mediates vascular relaxation by endothelial-derived nitric oxide and related nitrovasodilators (10, 16) (SI Text) both by activating MLCP (17) and by inhibiting the Rho/Rho kinase contractile pathway (18)(19)(20)(21).…”

mentioning

confidence: 99%

“…Mice in which the PKGI gene is inactivated in the germ line lack both PKGI isoforms throughout ontogeny. These mice are terminally ill when born (the majority die before 6 weeks of age) and have multiple cardiovascular, gastrointestinal, hematopoietic, and neurological defects that preclude complete investigation of most cardiovascular functions, including blood pressure (13,23). PKGI␣ and PKGI␤ both regulate VSMC tone through interactions with key VSMC contractile proteins mediated by their respective LZ domains (10,16,17,24).…”

mentioning

confidence: 99%

See 1 more Smart Citation

High blood pressure arising from a defect in vascular function

Michael

Surks

Wang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

127

146

View full text Add to dashboard Cite

Hypertension, a major cardiovascular risk factor and cause of mortality worldwide, is thought to arise from primary renal abnormalities. However, the etiology of most cases of hypertension remains unexplained. Vascular tone, an important determinant of blood pressure, is regulated by nitric oxide, which causes vascular relaxation by increasing intracellular cGMP and activating cGMPdependent protein kinase I (PKGI). Here we show that mice with a selective mutation in the N-terminal protein interaction domain of PKGI␣ display inherited vascular smooth muscle cell abnormalities of contraction, abnormal relaxation of large and resistance blood vessels, and increased systemic blood pressure. Renal function studies and responses to changes in dietary sodium in the PKGI␣ mutant mice are normal. These data reveal that PKGI␣ is required for normal VSMC physiology and support the idea that high blood pressure can arise from a primary abnormality of vascular smooth muscle cell contractile regulation, suggesting a new approach to the diagnosis and therapy of hypertension and cardiovascular diseases.cyclic nucleotides ͉ hypertension ͉ nitric oxide ͉ vascular biology ͉ vascular smooth muscle E levated blood pressure is a major risk factor for cardiovascular diseases and is responsible for widespread morbidity and mortality (1). Blood pressure is regulated by a variety of complex neurohumoral and mechanical signals that together determine systemic vascular tone and resistance (2, 3). The prevailing model for elevated blood pressure states that renal abnormalities of sodium handling cause volume expansion, increased systemic vascular resistance, and hypertension, and a large number of physiologic and genetic studies support this model and the central role of the renal renin-angiotensinaldosterone system in blood pressure regulation (4-8). Changes in vascular morphology and tone can increase vascular resistance and blood pressure (5), but the hypothesis that primary abnormalities of vascular smooth muscle tone can cause hypertension has not been sufficiently tested (6).Vascular smooth muscle contraction is initiated by both calcium-dependent and -independent mechanisms. Increases in intracellular calcium from receptor-or ion channel-activated pathways (2) lead to activation of myosin light chain kinase, which phosphorylates myosin light chains, activating myosin ATPase and increasing vascular smooth muscle cell (VSMC) contraction and vascular tone. The central calcium-independent pathway regulating VSMC tension is mediated by the GTPase RhoA and Rho kinase, which promote VSMC differentiation, stress fiber formation, and contraction, also increasing vascular tone (2, 7). Conversely, VSMC relaxation is mediated by activation of myosin light chain phosphatase (MLCP), which dephosphorylates myosin light chains to cause relaxation. The relative proportion of phosphorylated and dephosphorylated myosin light chains thus determines the state of VSMC tone (reviewed in ref.2). Nitric oxide, the most important endogenous vasodilator, cause...

show abstract

“…Renin and ␤-actin mRNA levels were measured by RNase protection assay as described previously (37). After phenol/chloroform extraction and ethanol precipitation, protected fragments were separated on an 8% polyacrylamide gel.…”

Section: Ribonuclease Protection Assay For Renin and ␤-Actinmentioning

confidence: 99%

Dominant Role of Prostaglandin E2 EP4 Receptor in Furosemide-Induced Salt-Losing Tubulopathy

Nüsing

Treude

Weißenberger

et al. 2005

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Increased formation of prostaglandin E 2 (PGE 2 ) is a key part of hyperprostaglandin E syndrome/antenatal Bartter syndrome (HPS/aBS), a renal disease characterized by NaCl wasting, water loss, and hyperreninism. Inhibition of PGE 2 formation by cyclo-oxygenase inhibitors significantly lowers patient mortality and morbidity. However, the pathogenic role of PGE 2 in HPS/aBS awaits clarification. Chronic blockade of the Na-K-2Cl co-transporter NKCC2 by diuretics causes symptoms similar to HPS/aBS and provides a useful animal model. In wild-type (WT) mice and in mice lacking distinct PGE 2 receptors (EP1 In summary, these findings demonstrate that the EP4 receptor mediates PGE 2 -induced renin secretion and that EP1, EP3, and EP4 receptors all contribute to enhanced PGE 2 -mediated salt and water excretion in the HPS/aBS model.

show abstract

Role of cGMP-kinase II in the control of renin secretion and renin expression.

Cited by 82 publications

References 60 publications

Angiotensin Subtype-2 Receptors Inhibit Renin Biosynthesis and Angiotensin II Formation

Angiotensin Subtype-2 Receptors Inhibit Renin Biosynthesis and Angiotensin II Formation

High blood pressure arising from a defect in vascular function

Dominant Role of Prostaglandin E2 EP4 Receptor in Furosemide-Induced Salt-Losing Tubulopathy

Contact Info

Product

Resources

About