Chronic blockade of endogenous atrial natriuretic polypeptide (ANP) by monoclonal antibody against ANP accelerates the development of hypertension in spontaneously hypertensive and deoxycorticosterone acetate-salt-hypertensive rats.

Itoh, Hiroshi; Nakao, Kazuwa; Mukoyama, Masashi; Yamada, Takayuki; Hosoda, Kiminori; Shirakami, Gotaro; Morii, Narito; Sugawara, Akira; Saito, Yoshihiko; Shiono, Satoshi

doi:10.1172/jci114134

Cited by 57 publications

(30 citation statements)

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“…23 In addition, we observed that intravenous injection of a 100 /xg dose of purified MAb KY-ANP-II inhibited the increase in plasma cyclic GMP induced by administration of exogenous ANP (20 /ig/kg i.v.) to the intact rat, 24 confirming the previous characterization of Itoh et al 21 The dose of MAb KY-ANP-II (0.55 fig) used in the current experiment is equivalent to the anti-ANP antibody contained in 0.55 jil of mouse ascites fluid. This is 0.5% of the peripheral intravenous dose (100 /il of ascites fluid) of this monoclonal antibody used in previous studies by Itoh et al 21 …”

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confidence: 89%

“…MAb KY-ANP-II recognizes human ANF-(99-126) and rat ANF-(99-126) equally and blocks the ability of both exogenous and endogenous ANP to elevate plasma cyclic GMP levels. 21 Intravenous administration of MAb KY-ANP-II has been shown to produce significant reductions in plasma cyclic GMP levels in stroke-prone SHR (SHRSP) and deoxycorticosterone acetate-salt rats, indicating that the antibody can block the activity of rat ANF-(99-126) in the intact rat. We purified IgG containing MAb KY-ANP-II from mouse ascites fluid (1 ml) with a protein A agarose column.…”

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confidence: 99%

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Atrial natriuretic peptide modulates baroreceptor reflex in spontaneously hypertensive rat.

et al. 1992

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Our previous studies have suggested that atrial natriuretic peptide in the caudal nucleus tractus solitarii is involved in the centrally mediated regulation of blood pressure in the salt-sensitive spontaneously hypertensive rat (SHR). The current study tested the hypothesis that endogenous atrial natriuretic peptide in the caudal nucleus tractus solitarii participates in baroreceptor reflex control of heart rate in this hypertensive model. Salt-sensitive SHR and control Wistar-Kyoto (WKY) rats maintained on basal (1%) salt intake were studied. Arterial baroreceptor reflex-mediated changes in heart rate were recorded in conscious unrestrained rats during phenylephrine 55 fig), or artificial cerebrospinal fluid vehicle (50 nl) was microinjected into the caudal nucleus tractus solitarii. Phenylephrine infusion was then repeated and mean arterial pressure and heart rate were monitored as before. The slope of the heart rate/mean arterial pressure relation was significantly less (p<0.05) in the salt-sensitive SHR than in the WKY control, indicating that baroreceptor reflex control of heart rate was blunted in this hypertensive model. Microinjection of atrial natriuretic peptide into the caudal nucleus tractus solitarii further blunted (p<0.05) baroreceptor reflex control of heart rate in salt-sensitive SHR but not in WKY rats. In contrast, microinjection of the monoclonal antibody enhanced the sensitivity of baroreceptor reflex control of heart rate in salt-sensitive SHR but not in WKY rats. These data suggest that endogenous atrial natriuretic peptide in the caudal nucleus tractus solitarii modulates baroreceptor reflex control of heart rate in salt-sensitive SHR bat not in WKY rats. 1 -3 In an anesthetized normotensive rat preparation, systemic administration of ANP has been shown to reduce sympathetic tone by a mechanism that involves a vagal afferent pathway and is partially buffered by arterial baroreceptor reflexes. "3 Intravenous administration of ANP to anesthetized normotensive rats with intact arterial baroreceptors resulted in decreased sympathetic outflow accompanied by reductions in blood pressure and heart rate (HR). Sinoaortic denervation exaggerated these responses to intravenous ANP, whereas vagal cooling to 0°C reversibly abolished the Received January 3, 1992; accepted in revised form May 12, 1992. sympathoinhibitory effect of intravenous ANP, indicating that this reflexry mediated action was dependent on afferent C-fiber activity in the vagus nerves.2 Further, recent studies have shown that circulating ANP in doses that have little effect on either blood pressure or HR exerts a complex modulatory effect on arterial baroreceptor reflexes in conscious normotensive rats. -5 ANP markedly potentiated reflex bradycardia but attenuated reflex tachycardia in response to intravenous boluses of phenylephrine and nitroprusside, respectively; it did not modify the pressor response to carotid occlusion. 4 Mechanisms that have been adduced to account for these effects of ANP include sensitization of cardiop...

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confidence: 89%

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confidence: 99%

Atrial natriuretic peptide modulates baroreceptor reflex in spontaneously hypertensive rat.

et al. 1992

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“…Several lines of evidence support the concept that ANP activates particulate guanylate cyclase and increases cyclic GMP accumulation in numerous cell types and tissues, including the vascular smooth muscle, endothelial cells, fibroblasts, and renal cells [44]. In the human and rat, an intravenous administration of ANP has been reported to elevate the plasma cGMP level [16,18]. Together, these findings suggest the significance of cyclic GMP as a second messenger and biological marker of ANP.…”

Section: Discussionmentioning

confidence: 80%

“…Recently, evidence has suggested that cardiovascular homeostasis is determined by a balance in cross-talk between the natriuretic peptide system and the angiotensin system [22]. Several investigations of ANP in cardiac tissues have been performed in the hypertensive animal model, including the spontaneously hypertensive rat (SHR) [3,19,29,31], SHR-stroke prone [2,29], deoxycorticosterone acetate (DOCA)-salt rat [18,34], and the Dahl salt sensitive rat with sodium chloride-induced hypertension [39]. To our knowledge, no data have been published on the plasma and heart ANP levels of THM in relation to hypertension by RAS.…”

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confidence: 99%

A-type Natriuretic Peptide Level in Hypertensive Transgenic Mice

et al. 2004

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A-type (atrial) natriuretic peptide (ANP) levels in heart and plasma were examined by immunohistochemistry, electron microscopy, and radioimmunoassay (RIA) in hypertensive transgenic mice (Tsukuba hypertensive mice; THM). Additionally, the ANP mRNA level in the heart was measured using real-time polymerase chain reaction (PCR) assay. The blood pressure and the ratio of heart weight to body weight in THM was significantly higher than those in the control mice (C57BL/6J). The number of ANPgranules and ANP immunoreactivity in the auricular cardiocytes were significantly lower in THM than in the control. Ultrastructurally, the ventricular cardiocytes in the THM occasionally had ANP-like granules, which were not present in the controls. Using RIA, the plasma, auricular, and ventricular ANP concentrations were significantly higher in THM than in the control, but there was no significant difference in plasma cyclic guanosine monophosphate (GMP) concentration between THM and the control. The ANP mRNA levels of the auricular and ventricular cardiocytes in the THM were siginificantly higher than those in the controls. The present study suggested that the ANP release system of the auricular cardiocytes in these transgenic mice is different from normal (control mice). Key words: A-type natriuretic peptide, hypertension, transgenic mice, cardiocyte in its etiology [21]. Several complex physiological systems affect blood pressure, including one that is mediated by the 28-amino acid A-type (atrial) natriuretic peptide (ANP) [13,21]. ANP is a circulating hormone with a wide range of biological effects, including natriuresis, diuresis and vasodilation, and it plays an important role in the regulation of blood pres-

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“…A third natriuretic peptide receptor with no intracellular guanylyl cyclase domain, dubbed the clearance receptor (C-receptor), is thought to be engaged in the receptor-mediated degradation of natriuretic peptides [2]. The ANP, BNP/GC-A system plays a pivotal role in the regulation of cardiovascular homeostasis, as demonstrated by their augmentation in various pathophysiological states such as heart failure [4][5][6][7][8], myocardial infarction [9, 10], cardiac hypertrophy [11,12], and hypertension [13][14][15]. In fact, ANP and BNP are cardiac hormones secreted primarily by the atrium and ventricle of the heart, respectively [8,15], with strong diuretic, natriuretic, and vasodilatory activities [4, 5, 8].…”

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Translational research of C-type natriuretic peptide (CNP) into skeletal dysplasias

Yasoda

Nakao

2010

Endocr J

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Abstract. By using transgenic and knockout mice, we have elucidated that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth. In humans, loss-of-function mutations in the gene coding for guanylyl cyclase-B (GC-B), the specific receptor for CNP, have been proved to be the cause of acromesomelic dysplasia, type Maroteaux, one form of human skeletal dysplasias. Following these results, we have started to translate the stimulatory effect of CNP on endochondral bone growth into the therapy for patients with skeletal dysplasias. We have shown that targeted overexpression of CNP in cartilage or systemic administration of CNP reverses the impaired skeletal growth of mice model of achondroplasia, the most common form of human skeletal dysplasias. Key words: C-type natriuretic peptide (CNP), Guanylyl cyclase-B (GC-B), Skeletal dysplasia, Achondroplasia, Translational researchThe nATriureTic peptide family consists of three structurally related peptides, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) [1]. The biological actions of natriuretic peptides are mediated by activation of two subtypes of membranous guanylyl cyclase (GC), GC-A and GC-B, followed by intracellular accumulation of cyclic GMP (cGMP) [2]. The rank order of potency to induce cGMP production via GC-A is ANP ≥ BNP >> CNP, while that via GC-B is CNP > ANP ≥ BNP [3]. Therefore, ANP and BNP serve as endogenous ligands for GC-A, whereas CNP is specific for GC-B. A third natriuretic peptide receptor with no intracellular guanylyl cyclase domain, dubbed the clearance receptor (C-receptor), is thought to be engaged in the receptor-mediated degradation of natriuretic peptides [2]. The ANP, BNP/GC-A system plays a pivotal role in the regulation of cardiovascular homeostasis, as demonstrated by their augmentation in various pathophysiological states such as heart failure [4][5][6][7][8], myocardial infarction [9, 10], cardiac hypertrophy [11,12], and hypertension [13][14][15]. In fact, ANP and BNP are cardiac hormones secreted primarily by the atrium and ventricle of the heart, respectively [8,15], with strong diuretic, natriuretic, and vasodilatory activities [4, 5, 8]. ANP and BNP are used in the treatment of heart failure [16,17] and serve as sensitive biochemical markers for heart failure and cardiac hypertrophy [6][7][8]. CNP, the third member of natriuretic peptide family, was first purified from porcine brain [18]. While CNP is the primary natriuretic peptide in the human brain [19], it is also produced by vascular endothelial cells [20][21][22] and macrophages [23], and is thought to act as an autocrine/paracrine regulator and as a neuropeptide [19]. Furthermore, analysis of genetically engineered mice of the CNP/GC-B system revealed that CNP and GC-B play a pivotal role in the regulation of endochondral bone growth.i. The growth promoting effect of the cnP/Gc-B system on endochondral bone growth I-1. Skeletal phenotypes of genetically engineered mice of the CNP/GC-B sys...

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Chronic blockade of endogenous atrial natriuretic polypeptide (ANP) by monoclonal antibody against ANP accelerates the development of hypertension in spontaneously hypertensive and deoxycorticosterone acetate-salt-hypertensive rats.

Cited by 57 publications

References 41 publications

Atrial natriuretic peptide modulates baroreceptor reflex in spontaneously hypertensive rat.

Atrial natriuretic peptide modulates baroreceptor reflex in spontaneously hypertensive rat.

A-type Natriuretic Peptide Level in Hypertensive Transgenic Mice

Translational research of C-type natriuretic peptide (CNP) into skeletal dysplasias

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