(RAPID COMMUNICATION) PLASMA LEVELS OF ATRIAL NATRIURETIC PEPTIDE IN HYPERTHYROIDISM
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SUMMARY We measured plasma atrial natriuretic peptide (ANP) levels in 17 patients with newly diagnosed thyrotoxicosis. ANP was elevated compared to a group of healthy controls and fell to normal after treatment. Plasma cyclic guanosine monophosphate was also raised in untreated patients. Elevated circulating levels of ANP may play a part in the haemodynamic changes of hyperthyroidism.Keywords:
Atrial natriuretic peptide
Cyclic guanosine monophosphate
Plasma levels
NPR2
NPR1
Background: The atrial natriuretic peptide (ANP) family is a complex system consisting of at least three polypeptides and at least three types of receptor. Each peptide interacts with different types of receptor at varying degrees of affinity. To determine if natriuretic peptide levels influence natriuretic peptide receptor expression and regulation, we examined the expression of guanylyl cyclase linked GC-A, GC-B and C-receptor in the lungs of mice with a mutation that inactivates the ANP gene (Nppa). Methods: The mRNA level of GC-A, GC-B and C-receptor in the lung were studied by ribonuclease protection assays (RPA). Results: Results of RPA showed that although the mRNA level of GC-A and GC-B of heterozygous ANP+/− was not different from wild type ANP+/+ mice, they were significantly higher in the homozygous mutant ANP−/− mice. In addition, C-receptor mRNA level in ANP+/− and ANP−/− was significantly lower than ANP+/+ mice. The C-receptor results were confirmed by receptor binding assays and affinity cross-linking studies. Conclusions: Taken together these data suggest that permanent removal of ANP from the natriuretic peptide system results in an up-regulation of GC-A and GC-B, and a corresponding down-regulation of C-receptor in the lung of proANP gene disrupted mice. We postulated that changes in the natriuretic peptide receptor population may result in chronic hypertension and cardiac hypertrophy in the ANP−/− mice.
Atrial natriuretic peptide
NPR2
NPR1
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Atrial natriuretic peptide
NPR2
NPR1
Cleavage (geology)
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Discovery of structurally related natriuretic peptide hormones: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) suggests that their role in control of body fluid and blood pressure homeostasis is complex. This complexity is further enhanced by the existence of at least three types of natriuretic peptide receptors, designated as Npra (GC-A), Nprb (GC-B), and Nprc (clearance receptor) (1-3). Although these three natriuretic peptides have highly homologous structure, they also have distinct sites of synthesis, bind to specific receptors, and probably elicit discrete biological functions (1-3). Both Npra and Nprb belong to the members of receptor guanylyl cyclase (GC) family, which produce their own second messenger cyclic guanosine monophosphate (cGMP). Production of cGMP in response to natriuretic peptides results from their binding to the extracellular domain of Npra or Nprb, which probably allosterically regulates an increased activity of the intracellular GC catalytic domain (3, 4). The extracellular domain of Npra and Nprb is homologous to Nprc which apparently does not contain a GC catalytic domain. ANP and BNP bind to Npra and CNP binds to Nprb; however, all three natriuretic peptides indiscriminately bind to Nprc (4). CNP is a natural ligand for Nprb and is the prominent cGMP-generating and the biologically active receptor in vascular smooth muscle cells (VSMC).
NPR2
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Cyclic guanosine monophosphate
Atrial natriuretic peptide
Second messenger system
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Atrial natriuretic peptide(ANP) is a member of the natriuretic peptide family. By binding with its receptor and thereafter activating guanylate cyclase, ANP increases intracellular cGMP level and hence produces biological effects. ANP exerts diuretic, natriuretic, vasorelaxant and antiproliferative actions and plays an important role in main-tening blood pressure, balance of fluid and sodium and also in the pathophysiology of cardiovascular diseases.
Atrial natriuretic peptide
NPR1
NPR2
Pathophysiology
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To elucidate the ligand-receptor relationship of the natriuretic peptide system, which comprises at least three endogenous ligands, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), and three receptors, the ANP-A receptor or guanylate cyclase-A (GC-A), the ANP-B receptor or guanylate cyclase-B (GC-B), and the clearance receptor (C-receptor), we characterized the receptor preparations from human, bovine, and rat tissues and cultured cells with the aid of the binding assay, Northern blot technique, and the cGMP production method. Using these receptor preparations, we examined the binding affinities of ANP, BNP, and CNP for the C-receptor and their potencies for cGMP production via the ANP-A receptor (GC-A) and the ANP-B receptor (GC-B). These analyses revealed the presence of a marked species difference in the receptor selectivity of the natriuretic peptide family, especially among BNPs. Therefore, we investigated the receptor selectivity of the natriuretic peptide family using the homologous assay system with endogenous ligands and receptors of the same species. The rank order of binding affinity for the C-receptor was ANP greater than CNP greater than BNP in both humans and rats. The rank order of potency for cGMP production via the ANP-A receptor (GC-A) was ANP greater than or equal to BNP much greater than CNP, but that via the ANP-B receptor (GC-B) was CNP greater than ANP greater than or equal to BNP. These findings on the receptor selectivity of the natriuretic peptide family provide a new insight into the understanding of the physiological and clinical implications of the natriuretic peptide system.
Atrial natriuretic peptide
NPR1
NPR2
Brain natriuretic peptide
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Atrial natriuretic peptide
NPR2
NPR1
Brain natriuretic peptide
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Atrial natriuretic peptide
NPR1
NPR2
Cyclic guanosine monophosphate
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HS-142-1, a specific nonpeptide antagonist for the atrial natriuretic peptide (ANP) receptor, equally blocked rat ANP (rANP)-, porcine brain natriuretic peptide-, or porcine C-type natriuretic peptide-stimulated GMP production in cultured bovine aortic smooth muscle (BASM) and bovine aortic endothelial (BAE) cells in a concentration-dependent fashion, at concentrations of 1-300 micrograms/ml. But, even at 300 micrograms/ml, HS-142-1 only weakly inhibited the specific binding of 125I-rANP to the BASM and BAE cells, where only a small portion of the binding sites are linked to guanylyl cyclase. Further, with BAE cell membranes, HS-142-1 recognized only the 135-kDa ANP receptor, which is thought from 125I-rANP affinity cross-linking studies to be the guanylyl cyclase-linked receptor. HS-142-1 also, if anything, inhibited the labeling of 135-kDa ANP receptors in the affinity cross-linking studies with BASM membranes, suggesting that a major portion of the 135-kDa ANP receptors are HS-142-1 insensitive and only a small portion of the 135-kDa ANP receptors are responsible for the blockade by HS-142-1 of GMP production in BASM cells. At a concentration of 100 micrograms/ml, HS-142-1 reversibly prevented ANP-induced relaxation of the isolated rabbit thoracic aorta induced to contract with 3 x 10(-7) M phenylephrine, but not the relaxation induced by sodium nitroprusside, isoproterenol, or papaverine. These results suggest that HS-142-1 specifically inhibits natriuretic peptide-induced vasorelaxation through the blockade of guanylyl cyclase-linked natriuretic peptide receptors. HS-142-1 thus will be a powerful tool for understanding the physiological roles, in vasculature, of natriuretic peptides, which contribute to the homeostasis of blood pressure and intravascular volume.
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NPR1
NPR2
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To elucidate the ligand-receptor relationship of the natriuretic peptide system, which comprises at least three endogenous ligands, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), and three receptors, the ANP-A receptor or guanylate cyclase-A (GC-A), the ANP-B receptor or guanylate cyclase-B (GC-B), and the clearance receptor (C-receptor), we characterized the receptor preparations from human, bovine, and rat tissues and cultured cells with the aid of the binding assay, Northern blot technique, and the cGMP production method. Using these receptor preparations, we examined the binding affinities of ANP, BNP, and CNP for the C-receptor and their potencies for cGMP production via the ANP-A receptor (GC-A) and the ANP-B receptor (GC-B). These analyses revealed the presence of a marked species difference in the receptor selectivity of the natriuretic peptide family, especially among BNPs. Therefore, we investigated the receptor selectivity of the natriuretic peptide family using the homologous assay system with endogenous ligands and receptors of the same species. The rank order of binding affinity for the C-receptor was ANP greater than CNP greater than BNP in both humans and rats. The rank order of potency for cGMP production via the ANP-A receptor (GC-A) was ANP greater than or equal to BNP much greater than CNP, but that via the ANP-B receptor (GC-B) was CNP greater than ANP greater than or equal to BNP. These findings on the receptor selectivity of the natriuretic peptide family provide a new insight into the understanding of the physiological and clinical implications of the natriuretic peptide system.
NPR1
Atrial natriuretic peptide
NPR2
Brain natriuretic peptide
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To investigate whether the increased nuchal translucency of trisomic fetuses is the consequence of heart failure by examining cardiac expression of atrial natriuretic peptide and brain natriuretic peptide genes.Cardiac atrial natriuretic peptide and brain natriuretic peptide messenger RNA (mRNA) levels were measured in fetal hearts from 15 pregnancies affected by trisomy 21 or 18 at 12-16 weeks' gestation and from 30 normal controls at 10-20 weeks.In normal fetuses, mRNA levels of atrial natriuretic peptide decreased, but levels of brain natriuretic peptide did not change significantly with gestation. In trisomic fetuses, mRNA levels of both atrial natriuretic peptide and brain natriuretic peptide were significantly higher than in gestational age-matched normal controls.These data demonstrate that atrial natriuretic peptide and brain natriuretic peptide genes are transcribed prenatally, and the findings in trisomic fetuses suggest that the increased translucency of trisomic fetuses may be the consequence of heart failure.
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Atrial natriuretic peptide
NPR1
Brain natriuretic peptide
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