Autocrine and paracrine actions of natriuretic peptides in the heart

D’Souza, Savio; Davis, Martin; Baxter, GF

doi:10.1016/j.pharmthera.2003.11.001

Cited by 187 publications

(148 citation statements)

References 161 publications

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“…Furthermore, chronic volume overload by an infrarenal aortocaval shunt in 8-week-old rats resulted in exaggerated cardiac hypertrophy in NPR-B ΔKC transgenic rats 6 weeks after surgery [27]. Although the affinity of CNP to NPRA is much less than to the NPRB receptor [28], and CNP does not increase cGMP accumulation in cells expressing human NPRA [11,29], we cannot finally exclude that transgenic CNP mediates part of its antihypertrophic effect via NPRA. Nevertheless, the combination of data from Langenickel et al and our findings provides clear evidence that the CNP/NPRB axis is implicated in the regulation of cardiomyocyte growth but not in cardiac fibrosis.…”

Section: Discussionmentioning

confidence: 90%

“…However, the possible mechanisms for the cardioprotective effects of the three natriuretic peptides on I/R seem to be controversial. NPRC activation is thought to be responsible for the cardioprotective role of CNP as mentioned above, and the selective agonist of NPRC (cANF [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] ) also reduces infarct size and maintains coronary perfusion pressure [12]. Studies of ANP and BNP effects show the involvement of cGMP generated via the NPRA receptor in the reduction of infarct size [24,25].…”

Section: Discussionmentioning

confidence: 99%

“…Since Wei and colleagues first confirmed the presence of CNP within the myocardium by immunohistochemistry and radioimmunoassay [10], accumulating evidence suggests that CNP exhibits important autocrine and paracrine functions within the heart and coronary circulation [11]. Hobbs et al demonstrated that, in addition to interacting with its receptor NPRB, endothelium-derived CNP is involved in the regulation of rat coronary circulation via the activation of NPRC [12].…”

Section: Introductionmentioning

confidence: 99%

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Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice

Wang

Waard

Sterner-Kock

et al. 2007

European J of Heart Fail

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Objective: Infused C-type natriuretic peptide (CNP) was recently found to play a cardioprotective role in preventing myocardial ischaemia/ reperfusion (I/R) injury and improving cardiac remodelling after myocardial infarction (MI) in rats. Our study aimed to investigate the effect of cardiomyocyte-specific CNP over-expression on I/R injury and MI in transgenic mice. Methods and results:We generated transgenic (TG) mice over-expressing CNP in cardiomyocytes. Elevated CNP expression on RNA and protein levels was demonstrated by RNase-protection assay and radioimmunoassay. Male TG mice and age-matched wild-type (WT) littermates were subjected to 1-hour global myocardial ischaemia and 23 h of reperfusion or permanent ligation of the coronary artery for 3 weeks.Infarct size did not differ between the WT and TG groups in mice subjected to I/R. In mice that underwent permanent ligation of coronary arteries, both left and right ventricular hypertrophy were prevented by CNP over-expression 3 weeks post-MI. Histological analysis revealed less necrosis, muscular degeneration and inflammation in infarcted TG mice. Impairment of cardiac function was less pronounced in transgenic animals than in the wild-type controls. Conclusions: Over-expression of CNP in cardiomyocytes does not affect I/R-induced infarct size but prevents cardiac hypertrophy induced by MI. Therefore, CNP may represent a potent therapeutic target for the treatment of patients with cardiac hypertrophy induced by myocardial infarction or other aetiology.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice

Wang

Waard

Sterner-Kock

et al. 2007

European J of Heart Fail

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“…Natriuretic peptides function through the membrane-associated receptors with associated particulate guanylyl cyclase domains that can elevate the intracellular level of cyclic GMP. The two subtypes of these receptors (NPR-A and NPR-B) that elevate cyclic GMP are widely expressed in the cardiovascular system [21]. Elevation of intracellular cyclic GMP concentration can be demonstrated in all tissues and cell types expressing NPR-A or NPR-B following exposure to natriuretic peptides [21].…”

Section: Discussionmentioning

confidence: 99%

Chronic nitrates blunt the effects of not only nitric oxide but also natriuretic peptides in cardiac myocytes

Tan¹,

Zhang²,

Anyadike³

et al. 2007

Pharmacological Research

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Abstractexposure to nitrates causes tachyphylaxis to nitric oxide (NO), which reduces the effects of the second messenger cyclic GMP. We tested the hypothesis that prolonged exposure to NO would also blunt the effects of natriuretic peptides. Cardiac myocytes were isolated from control (N=7) and chronic nitroglycerin (patched, N=7) rabbits. Patched animals received a transdermal nitroglycerin patch (0.3 mg/hr for 5 days). Myocyte function was determined at baseline, after CNP (C-type natriuretic peptide, 10 −8 and 10 −7 M) or BNP (Brain natriuretic peptide, 10 −8 and 10 −7 M) or SNAP (S-nitroso-N-acetyl-penicilliamine, a NO donor, 10 −6 and 10 −5 M) followed by KT5823 (a cyclic GMP protein kinase inhibitor, 10 −6 M). Soluble and particulate guanylyl cyclase activities were measured in vitro and phosphoprotein analysis was performed. In control animals, CNP 10 −8 M (5.14±0.5%) and 10 −7 M (4.4±0.7%) significantly reduced percentage shortening from baseline (6.1±1.6%). KT5823 restored percentage shortening to 4.9±0.8%. Similar data were obtained with BNP and SNAP. In patched animals, CNP, BNP, SNAP had no significant effects on percentage shortening. The data on maximal rate of shortening and relaxation were consistent with these results. Guanylyl cyclase activities were not different in the control and patched animals. The myocytes from control and patched animals had similar protein phosphorylation patterns. Our data suggested that in addition to NO, the responses to both natriuretic peptides were downregulated after chronic exposure to nitroglycerin, but these effects were not due to changes in either guanylyl cyclase or cyclic GMP protein kinase, suggesting an altered downstream pathway.

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“…Atrial natriuretic peptide (ANP), a 27-aa peptide hormone with potent vasodilatory, natriuretic, diuretic, and antihypertrophic effects, is an attractive candidate gene product for antihypertensive therapy (4,5). Studies involving the infusion of synthetic ANP to humans with HTN have demonstrated significant decreases in blood pressure and brisk natriuresis͞diuresis associated with peptide administration (6,7).…”

mentioning

confidence: 99%

Regulatable atrial natriuretic peptide gene therapy for hypertension

Schillinger

Tsai

Taffet

et al. 2005

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

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Hypertension (HTN) is a disease that begins with dysfunctional renal-sodium excretion and progresses to a syndrome of highly elevated systolic, diastolic, and mean arterial pressures. Inadequacies in the therapy of HTN have led to the investigation of the gene therapy of this disease by using systemic overproduction of vasodilatory peptides, such as atrial natriuretic peptide (ANP). However, gene-therapy approaches to HTN using ANP are limited by the need for long-term ANP gene expression and, most important, control of ANP gene expression. Here, we introduce a helperdependent adenoviral vector carrying the mifepristone (Mfp)-inducible gene-regulatory system to control in vivo ANP expression. In the BPH͞2 mouse model of HTN, Mfp-inducible ANP expression was seen for a period of >120 days after administration of vector. Physiological effects of ANP, including decreased systolic blood pressure, increased urinary cGMP output, and decreases in heart weight as a percentage of body weight were also under the control of Mfp. Given these capabilities, this vector represents a paradigm for the gene therapy of HTN. adenovirus ͉ mifepristone-inducible H ypertension (HTN) is a disease that is characterized by chronically elevated arterial blood pressure that affects Ϸ25-35% of the population in developed countries, and it is one of the leading causes of morbidity and mortality in adults (1). Development of HTN is likely to involve defects in renal-sodium handling that are exacerbated by maladaptive activation of neurohormonal compensatory mechanisms. The morbidity and mortality caused by the hypertensive state are a consequence of detrimental effects that manifest predominantly in the heart, brain, and kidney and are referred to collectively as hypertensive end-organ disease. Typically, endorgan disease involves pathological left-ventricular hypertrophy, a propensity toward cerebrovascular accidents, and accelerated renal atherosclerosis (1, 2).The current therapy of HTN has been rationally designed to address the recognized causes of hypertensive pathophysiology, including impaired urinary-sodium excretion and neurohormonal compensatory-mechanism activation. Also, in recognition of the fact that hypertensive end-organ disease represents the true danger of chronically elevated arterial blood pressure, the main goals of antihypertensive therapy have evolved to include a reduction in blood pressure as well as prevention of cardiovascular, cerebrovascular, and renal pathology associated with elevated blood pressure (2, 3). However, a multitude of studies have revealed that no available drug therapy for HTN has the capability to cure the hypertensive state or reverse or prevent the pathological changes associated with hypertensive end-organ disease fully (2). As a result, therapeutic approaches to HTN involving gene therapy have been of recent interest.Atrial natriuretic peptide (ANP), a 27-aa peptide hormone with potent vasodilatory, natriuretic, diuretic, and antihypertrophic effects, is an attractive candidate gene product f...

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Autocrine and paracrine actions of natriuretic peptides in the heart

Cited by 187 publications

References 161 publications

Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice

Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice

Chronic nitrates blunt the effects of not only nitric oxide but also natriuretic peptides in cardiac myocytes

Regulatable atrial natriuretic peptide gene therapy for hypertension

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