Blunted cGMP response to agonists and enhanced glomerular cyclic 3',5'-nucleotide phosphodiesterase activities in experimental congestive heart failure

Thanom Supaporn, Sharon M. Sandberg, Daniel Dean Borgeson, Denise M. Heublein, Andreas Luchner, Chi Ming Wei, Thomas P. Dousa, John C Jr. Burnett

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The natriuretic peptide (NP) and nitric oxide (NO) systems are activated in congestive heart failure (CHF), resulting in increased synthesis of cGMP, which serves as a second messenger for both humoral systems. These two regulatory systems play functional roles in the preservation of glomerular filtration rate (GFR) and sodium excretion in both acute and chronic CHF. A progressive decline in glomerular responsiveness to atrial natriuretic peptide (ANP) characterizes the terminal stage of chronic CHF despite elevation of plasma ANP. Phosphodiesterase isozymes (PDEs) are integral factors in determining cellular content and accumulation of cGMP, and up-regulation of PDE activity could participate in the glomerular resistance to ANP in severe CHF. To date, characterization of possible alteration of glomerular PDE isoxyme activities in CHF is unknown, as is the in vitro glomerular response to the nitric oxide-soluble guanylyl cyclase pathway. We, therefore, first determined cGMP generation in response to particulate and soluble guanylyl cyclase activation by ANP and sodium nitroprusside (SNP) in isolated glomeruli from normal (N = 6) and CHF dogs (N = 5) in which CHF was induced by rapid ventricular pacing for 18 to 28 days. Secondly, we explored the presence of major PDE isoxymes in glomeruli isolated from the control and CHF dogs. When ANP or SNP (10-10 to 10-4 M) were incubated with the suspension of isolated glomeruli, cGMP accumulation was lower by -72 to -96% with ANP and -42 to -77% with SNP in all glomerular medias obtained from CHF compared to controls. PDE hydrolyzing activity of both cAMP and cGMP were higher in the glomerular homogenates obtained from the kidneys of the CHF group (N = 5) compared to those of the control group (N = 5). We conclude that in severe chronic experimental CHF, glomerular cGMP accumulation decreases in response to both ANP and SNP, and CHF is characterized by enhanced cAMP- and cGMP-PDE activities that may participate in glomerular maladaptation to this cardiovascular syndrome.

Original languageEnglish (US)
Pages (from-to)1718-1725
Number of pages8
JournalKidney International
Volume50
Issue number5
StatePublished - Nov 1996

Fingerprint

3',5'-Cyclic-AMP Phosphodiesterases
Heart Failure
Atrial Natriuretic Factor
Phosphoric Diester Hydrolases
Isoenzymes
Nitroprusside
Nitric Oxide
Dogs
Natriuretic Peptides
Second Messenger Systems
Glomerular Filtration Rate

ASJC Scopus subject areas

  • Nephrology

Cite this

Blunted cGMP response to agonists and enhanced glomerular cyclic 3',5'-nucleotide phosphodiesterase activities in experimental congestive heart failure. / Supaporn, Thanom; Sandberg, Sharon M.; Borgeson, Daniel Dean; Heublein, Denise M.; Luchner, Andreas; Wei, Chi Ming; Dousa, Thomas P.; Burnett, John C Jr.

In: Kidney International, Vol. 50, No. 5, 11.1996, p. 1718-1725.

Research output: Contribution to journalArticle

Supaporn, Thanom ; Sandberg, Sharon M. ; Borgeson, Daniel Dean ; Heublein, Denise M. ; Luchner, Andreas ; Wei, Chi Ming ; Dousa, Thomas P. ; Burnett, John C Jr. / Blunted cGMP response to agonists and enhanced glomerular cyclic 3',5'-nucleotide phosphodiesterase activities in experimental congestive heart failure. In: Kidney International. 1996 ; Vol. 50, No. 5. pp. 1718-1725.
@article{848af28579214623918a6abc533e1892,
title = "Blunted cGMP response to agonists and enhanced glomerular cyclic 3',5'-nucleotide phosphodiesterase activities in experimental congestive heart failure",
abstract = "The natriuretic peptide (NP) and nitric oxide (NO) systems are activated in congestive heart failure (CHF), resulting in increased synthesis of cGMP, which serves as a second messenger for both humoral systems. These two regulatory systems play functional roles in the preservation of glomerular filtration rate (GFR) and sodium excretion in both acute and chronic CHF. A progressive decline in glomerular responsiveness to atrial natriuretic peptide (ANP) characterizes the terminal stage of chronic CHF despite elevation of plasma ANP. Phosphodiesterase isozymes (PDEs) are integral factors in determining cellular content and accumulation of cGMP, and up-regulation of PDE activity could participate in the glomerular resistance to ANP in severe CHF. To date, characterization of possible alteration of glomerular PDE isoxyme activities in CHF is unknown, as is the in vitro glomerular response to the nitric oxide-soluble guanylyl cyclase pathway. We, therefore, first determined cGMP generation in response to particulate and soluble guanylyl cyclase activation by ANP and sodium nitroprusside (SNP) in isolated glomeruli from normal (N = 6) and CHF dogs (N = 5) in which CHF was induced by rapid ventricular pacing for 18 to 28 days. Secondly, we explored the presence of major PDE isoxymes in glomeruli isolated from the control and CHF dogs. When ANP or SNP (10-10 to 10-4 M) were incubated with the suspension of isolated glomeruli, cGMP accumulation was lower by -72 to -96{\%} with ANP and -42 to -77{\%} with SNP in all glomerular medias obtained from CHF compared to controls. PDE hydrolyzing activity of both cAMP and cGMP were higher in the glomerular homogenates obtained from the kidneys of the CHF group (N = 5) compared to those of the control group (N = 5). We conclude that in severe chronic experimental CHF, glomerular cGMP accumulation decreases in response to both ANP and SNP, and CHF is characterized by enhanced cAMP- and cGMP-PDE activities that may participate in glomerular maladaptation to this cardiovascular syndrome.",
author = "Thanom Supaporn and Sandberg, {Sharon M.} and Borgeson, {Daniel Dean} and Heublein, {Denise M.} and Andreas Luchner and Wei, {Chi Ming} and Dousa, {Thomas P.} and Burnett, {John C Jr.}",
year = "1996",
month = "11",
language = "English (US)",
volume = "50",
pages = "1718--1725",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Blunted cGMP response to agonists and enhanced glomerular cyclic 3',5'-nucleotide phosphodiesterase activities in experimental congestive heart failure

AU - Supaporn, Thanom

AU - Sandberg, Sharon M.

AU - Borgeson, Daniel Dean

AU - Heublein, Denise M.

AU - Luchner, Andreas

AU - Wei, Chi Ming

AU - Dousa, Thomas P.

AU - Burnett, John C Jr.

PY - 1996/11

Y1 - 1996/11

N2 - The natriuretic peptide (NP) and nitric oxide (NO) systems are activated in congestive heart failure (CHF), resulting in increased synthesis of cGMP, which serves as a second messenger for both humoral systems. These two regulatory systems play functional roles in the preservation of glomerular filtration rate (GFR) and sodium excretion in both acute and chronic CHF. A progressive decline in glomerular responsiveness to atrial natriuretic peptide (ANP) characterizes the terminal stage of chronic CHF despite elevation of plasma ANP. Phosphodiesterase isozymes (PDEs) are integral factors in determining cellular content and accumulation of cGMP, and up-regulation of PDE activity could participate in the glomerular resistance to ANP in severe CHF. To date, characterization of possible alteration of glomerular PDE isoxyme activities in CHF is unknown, as is the in vitro glomerular response to the nitric oxide-soluble guanylyl cyclase pathway. We, therefore, first determined cGMP generation in response to particulate and soluble guanylyl cyclase activation by ANP and sodium nitroprusside (SNP) in isolated glomeruli from normal (N = 6) and CHF dogs (N = 5) in which CHF was induced by rapid ventricular pacing for 18 to 28 days. Secondly, we explored the presence of major PDE isoxymes in glomeruli isolated from the control and CHF dogs. When ANP or SNP (10-10 to 10-4 M) were incubated with the suspension of isolated glomeruli, cGMP accumulation was lower by -72 to -96% with ANP and -42 to -77% with SNP in all glomerular medias obtained from CHF compared to controls. PDE hydrolyzing activity of both cAMP and cGMP were higher in the glomerular homogenates obtained from the kidneys of the CHF group (N = 5) compared to those of the control group (N = 5). We conclude that in severe chronic experimental CHF, glomerular cGMP accumulation decreases in response to both ANP and SNP, and CHF is characterized by enhanced cAMP- and cGMP-PDE activities that may participate in glomerular maladaptation to this cardiovascular syndrome.

AB - The natriuretic peptide (NP) and nitric oxide (NO) systems are activated in congestive heart failure (CHF), resulting in increased synthesis of cGMP, which serves as a second messenger for both humoral systems. These two regulatory systems play functional roles in the preservation of glomerular filtration rate (GFR) and sodium excretion in both acute and chronic CHF. A progressive decline in glomerular responsiveness to atrial natriuretic peptide (ANP) characterizes the terminal stage of chronic CHF despite elevation of plasma ANP. Phosphodiesterase isozymes (PDEs) are integral factors in determining cellular content and accumulation of cGMP, and up-regulation of PDE activity could participate in the glomerular resistance to ANP in severe CHF. To date, characterization of possible alteration of glomerular PDE isoxyme activities in CHF is unknown, as is the in vitro glomerular response to the nitric oxide-soluble guanylyl cyclase pathway. We, therefore, first determined cGMP generation in response to particulate and soluble guanylyl cyclase activation by ANP and sodium nitroprusside (SNP) in isolated glomeruli from normal (N = 6) and CHF dogs (N = 5) in which CHF was induced by rapid ventricular pacing for 18 to 28 days. Secondly, we explored the presence of major PDE isoxymes in glomeruli isolated from the control and CHF dogs. When ANP or SNP (10-10 to 10-4 M) were incubated with the suspension of isolated glomeruli, cGMP accumulation was lower by -72 to -96% with ANP and -42 to -77% with SNP in all glomerular medias obtained from CHF compared to controls. PDE hydrolyzing activity of both cAMP and cGMP were higher in the glomerular homogenates obtained from the kidneys of the CHF group (N = 5) compared to those of the control group (N = 5). We conclude that in severe chronic experimental CHF, glomerular cGMP accumulation decreases in response to both ANP and SNP, and CHF is characterized by enhanced cAMP- and cGMP-PDE activities that may participate in glomerular maladaptation to this cardiovascular syndrome.

UR - http://www.scopus.com/inward/record.url?scp=0029988221&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029988221&partnerID=8YFLogxK

M3 - Article

C2 - 8914042

AN - SCOPUS:0029988221

VL - 50

SP - 1718

EP - 1725

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 5

ER -