Faculty Opinions recommendation of Inhibition of TRPC6 channel activity contributes to the antihypertrophic effects of natriuretic peptides-guanylyl cyclase-A signaling in the heart.

2010 ◽  
Author(s):  
David Van Wagoner
Keyword(s):  
Guanylyl Cyclase ◽  
Natriuretic Peptides ◽  
Channel Activity ◽  
Trpc6 Channel

scholarly journals Inhibition of TRPC6 Channel Activity Contributes to the Antihypertrophic Effects of Natriuretic Peptides-Guanylyl Cyclase-A Signaling in the Heart

2010 ◽  
Vol 106 (12) ◽  
pp. 1849-1860 ◽  
Author(s):  
Hideyuki Kinoshita ◽  
Koichiro Kuwahara ◽  
Motohiro Nishida ◽  
Zhong Jian ◽  
Xianglu Rong ◽  
...  
Keyword(s):  
Guanylyl Cyclase ◽  
Natriuretic Peptides ◽  
Channel Activity ◽  
Trpc6 Channel

scholarly journals Molecular and genetic aspects of guanylyl cyclase natriuretic peptide receptor-A in regulation of blood pressure and renal function

2018 ◽  
Vol 50 (11) ◽  
pp. 913-928 ◽  
Author(s):  
Kailash N. Pandey
Keyword(s):  
Blood Pressure ◽  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Natriuretic Peptides ◽  
Molecular Mechanisms ◽  
Phenotypic Characterization ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A ◽  
Regulation Of Blood Pressure

Natriuretic peptides (NPs) exert diverse effects on several biological and physiological systems, such as kidney function, neural and endocrine signaling, energy metabolism, and cardiovascular function, playing pivotal roles in the regulation of blood pressure (BP) and cardiac and vascular homeostasis. NPs are collectively known as anti-hypertensive hormones and their main functions are directed toward eliciting natriuretic/diuretic, vasorelaxant, anti-proliferative, anti-inflammatory, and anti-hypertrophic effects, thereby, regulating the fluid volume, BP, and renal and cardiovascular conditions. Interactions of NPs with their cognate receptors display a central role in all aspects of cellular, biochemical, and molecular mechanisms that govern physiology and pathophysiology of BP and cardiovascular events. Among the NPs atrial and brain natriuretic peptides (ANP and BNP) activate guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) and initiate intracellular signaling. The genetic disruption of Npr1 (encoding GC-A/NPRA) in mice exhibits high BP and hypertensive heart disease that is seen in untreated hypertensive subjects, including high BP and heart failure. There has been a surge of interest in the NPs and their receptors and a wealth of information have emerged in the last four decades, including molecular structure, signaling mechanisms, altered phenotypic characterization of transgenic and gene-targeted animal models, and genetic analyses in humans. The major goal of the present review is to emphasize and summarize the critical findings and recent discoveries regarding the molecular and genetic regulation of NPs, physiological metabolic functions, and the signaling of receptor GC-A/NPRA with emphasis on the BP regulation and renal and cardiovascular disorders.

scholarly journals Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation

2010 ◽  
Vol 48 (4) ◽  
pp. 713-724 ◽  
Author(s):  
Norimichi Koitabashi ◽  
Takeshi Aiba ◽  
Geoffrey G. Hesketh ◽  
Janelle Rowell ◽  
Manling Zhang ◽  
...  
Keyword(s):  
Cyclic Gmp ◽  
Channel Activity ◽  
Dependent Inhibition ◽  
Nfat Activation ◽  
Trpc6 Channel

Regulation of cGMP by soluble and particulate guanylyl cyclases in cultured human airway smooth muscle

1997 ◽  
Vol 273 (4) ◽  
pp. L807-L813 ◽  
Author(s):  
Ahmed M. Hamad ◽  
Simon Range ◽  
Elaine Holland ◽  
Alan J. Knox
Keyword(s):  
Smooth Muscle ◽  
Natriuretic Peptide ◽  
Airway Smooth Muscle ◽  
Guanylyl Cyclase ◽  
Natriuretic Peptides ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
Guanylyl Cyclases ◽  
Human Airway ◽  
Type V

Although guanosine 3′,5′-cyclic monophosphate (cGMP) acts as a relaxant second messenger, the regulation of intracellular cGMP has not been comprehensively studied in human airway smooth muscle. We studied the production of cGMP by cultured human airway smooth muscle cells (HASMC) after stimulation with activators of soluble guanylyl cyclase [sodium nitroprusside (SNP) and S-nitroso- N-acetylpenicillamine (SNAP)] and particulate guanylyl cyclase [atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Escherichia coli heat stable enterotoxin (STa)]. cGMP was measured by enzyme-linked immunosorbent assay. Both SNP (10−6 to 10−3 M) and SNAP (10−6 to 10−3 M) caused concentration-dependent elevation of cGMP in the presence of the nonselective phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (10−3 M), with cGMP increasing 6- and 15-fold in response to SNP and SNAP, respectively, at the highest concentration tested (10−3 M). The increases in cGMP in response to SNP (5 × 10−5 M) and SNAP (10−5 M) were inhibited by hemoglobin (Hb; 5 × 10−5 M), a nitric oxide scavenger, and methylene blue (MB; 5 × 10−4 M), an inhibitor of guanylyl cyclase. cGMP accumulation after SNAP was abolished by both Hb and MB. The response to SNP was inhibited by 79% with Hb and was abolished with MB. ANP, BNP, and CNP (10−9 to 10−5 M) + phosphoramidon (10−6 M) caused a concentration-dependent elevation in cGMP with an order of potency ANP > BNP > CNP. cGMP formation in the presence of the highest concentration of the most potent natriuretic peptide (10−5 M ANP) was two- to threefold greater than with the highest concentration of SNAP. The increase in cGMP seen with natriuretic peptides was similar in the presence or absence of phosphoramidon, a neutral endopeptidase (NEP) inhibitor, suggesting that NEP is not playing a role in modulating the effect of natriuretic peptides in HASMC. STa (400 IU/ml) had no effect on cGMP levels. SNAP- and ANP-induced cGMP accumulation was increased by the selective type V PDE inhibitors SKF-96231 and zaprinast, suggesting that type V PDE is responsible for cGMP breakdown in HASMC. These results suggest that cultured HASMC contain both soluble and particulate guanylyl cyclases. The order of potency of the natriuretic peptides ANP > BNP > CNP suggests that type A particulate membrane-bound guanylate cyclase predominates.

Chronic carbon monoxide exposure of hypoxic rats increases in vitro sensitivity of pulmonary artery smooth muscle

2003 ◽  
Vol 81 (7) ◽  
pp. 711-719 ◽  
Author(s):  
Eric Dubuis ◽  
Mathieu Gautier ◽  
Alexandre Melin ◽  
Manuel Rebocho ◽  
Catherine Girardin ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Channel Activity ◽  
Pulmonary Vasodilation ◽  
Pulmonary Artery Smooth Muscle ◽  
First Time

Exogenous carbon monoxide (CO) induces pulmonary vasodilation by acting directly on pulmonary artery (PA) smooth muscle cells. We investigated the contribution of K+ channels and soluble guanylyl cyclase to the regulation of PA tone by acute CO in chronic hypoxic rats (3 weeks at 0.5 atm (1 atm = 101.325 kPa); hypoxic) and in chronic hypoxic rats exposed to exogenous CO (3 weeks at 0.5 atm + 50 ppm CO; hypoxic-CO). Acute CO induced relaxation in PA rings from all animals. However, the amplitude of CO relaxation was significantly decreased in hypoxic rings and increased in hypoxic-CO rings. This different effect occurred with a decrease and an increase of pD2, respectively, in hypoxic and hypoxic-CO rings. We showed a positive relation between the percentage of inhibition of CO relaxation by a blocker of K+ channels and the increase of CO sensitivity. Thus, we showed for the first time that chronic hypoxia decreases acute CO sensitivity, which in contrast, increases in the presence of chronic CO. The present study provides initial evidence of a link between increased K+-channel activity and CO sensitivity.Key words: K+-channel blocker, tetraethylammonium, soluble guanylyl cyclase, gasotransmitter.

Regulation of the natriuretic peptide system in rat uterus during the estrous cycle

1997 ◽  
Vol 153 (3) ◽  
pp. 345-355 ◽  
Author(s):  
A M Reis ◽  
M Jankowski ◽  
S Mukaddam-Daher ◽  
J Tremblay ◽  
T-V Dam ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Natriuretic Peptides ◽  
Uterine Tissue ◽  
Rt Pcr ◽  
Tissue Slices ◽  
Peptide System ◽  
Uterine Glands ◽  
Hydromineral Balance

Abstract Uterine natriuretic peptides may be involved in the alterations that occur in the uterus during the estrous cycle through its role in hydromineral balance. The following studies were performed to determine whether uterine natriuretic peptides and receptors follow a cyclic pattern during the estrous cycle. The results obtained show that atrial natriuretic peptide (ANP) content in rat uterine tissue was low in proestrus (8·5 ± 2·6 pg/g) and significantly increased (P<0·001) in estrus (71·5 ± 16·6 pg/g), metestrus (82·6 ± 19·7 pg/g) and diestrus (91·0 ± 19·4 pg/g), whereas plasma ANP was not altered during the cycle. Similarly, measurement of uterine ANP mRNA by reverse transcribed polymerase chain reaction (RT-PCR) indicated lowest levels of ANP mRNA at proestrus. Measurement of C-type natriuretic peptide (CNP) by a specific and sensitive radioimmunoassay revealed that uterine CNP also varies with the estrous cycle. Uterine CNP was low in diestrus (143·2 ± 22·4 pg/mg protein) as compared with proestrus, estrus and metestrus (305·3 ± 51·5, 267·5 ± 44·9, 291 ± 41·2 pg/mg protein respectively, P<0·05). Autoradiography performed on uterine tissue slices localized natriuretic peptide receptors to myometrial smooth muscle layers and to endometrial uterine glands. High binding of 125I-ANP was observed in proestrus and estrus with 60–75% decreases during metestrus and diestrus. Binding of 125I-tyr0CNP to uterine slices was also high during proestrus, but declined by 35% at estrus, metestrus and diestrus. The alterations in the receptors were also observed at the level of synthesis. RT-PCR detection of guanylyl cyclase A (GC-A) receptor mRNA and guanylyl cyclase B (GC-B) mRNA showed high signals at proestrus but 4- and 2-fold reductions respectively at metestrus and diestrus. In conclusion, variations in uterine ANP and CNP and their receptors during the rat estrous cycle imply the involvement of the natriuretic peptides in uterine hydromineral balance and myometrial motor activity. Journal of Endocrinology (1997) 153, 345–355

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