Blood pressure and fluid-electrolyte balance in mice with reduced or absent ANP

John, Simon W. M.; Veress, A. T.; Honrath, U.; Chong, Chee Keong; Peng, L.‐H.; Smithies, Oliver; Sonnenberg, H.

doi:10.1152/ajpregu.1996.271.1.r109

Cited by 66 publications

(69 citation statements)

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“…50 The important role of the ANP/GC-A system in the physiological regulation of arterial blood pressure/volume has been emphasized in different genetic mouse models. Targeted deletion of the peptide (ANP Ϫ/Ϫ ) or its receptor (GC-A Ϫ/Ϫ ), leads to severe, chronic arterial hypertension, cardiac hypertrophy, and sudden death [51][52][53][54] (Figure 2). In contrast, overexpression of ANP or GC-A elicits a "dosedependent" fall in arterial blood pressure.…”

Section: Anp Bnp and Their Receptor Gc-amentioning

confidence: 99%

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

Kühn

2003

Circulation Research

241

161

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Abstract-Besides soluble guanylyl cyclase (GC), the receptor for NO, there are at least seven plasma membrane enzymes that synthesize the second-messenger cGMP. All membrane GCs (GC-A through GC-G) share a basic topology, which consists of an extracellular ligand binding domain, a short transmembrane region, and an intracellular domain that contains the catalytic (GC) region. Although the presence of the extracellular domain suggests that all these enzymes function as receptors, specific ligands have been identified for only three of them (GC-A through GC-C). GC-A mediates the endocrine effects of atrial and B-type natriuretic peptides regulating arterial blood pressure and volume homeostasis and also local antihypertrophic actions in the heart. GC-B is a specific receptor for C-type natriuretic peptide, having more of a paracrine function in vascular regeneration and endochondral ossification. GC-C mediates the effects of guanylin and uroguanylin on intestinal electrolyte and water transport and on epithelial cell growth and differentiation. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have an important role in phototransduction. Finally, the functions of GC-D (located in the olfactory neuroepithelium) and GC-G (expressed in highest amounts in lung, intestine, and skeletal muscle) are completely unknown. This review discusses the structure and functions of membrane GCs, with special emphasis on the physiological endocrine and cardiac functions of GC-A, the regulation of hormone-dependent GC-A activity, and the relevance of alterations of the atrial natriuretic peptide/GC-A system to cardiovascular diseases. (Circ Res. 2003;93:700-709.)

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Section: Anp Bnp and Their Receptor Gc-amentioning

confidence: 99%

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

Kühn

2003

Circulation Research

241

161

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“…In particular, mice lacking endothelial NO synthase (eNOS) (12), ANP (13), or the ANP receptor, GC-A (14,15), exhibit drastic arterial hypertension, experimental observations that emphasize the importance of cGMP-dependent vasodilation in cardiovascular homeostasis.…”

mentioning

confidence: 99%

Increased Sensitivity to Endothelial Nitric Oxide (NO) Contributes to Arterial Normotension in Mice with Vascular Smooth Muscle-selective Deletion of the Atrial Natriuretic Peptide (ANP) Receptor

Sabrane

Gambaryan

Brandes

et al. 2003

Journal of Biological Chemistry

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Atrial natriuretic peptide (ANP) plays a key regulatory role in arterial blood pressure homeostasis. We recently generated mice with selective deletion of the ANP receptor, guanylyl cyclase-A (GC-A), in vascular smooth muscle (SMC GC-A knockout (KO) mice) and reported that resting arterial blood pressure was completely normal in spite of clear abolition of the direct vasodilating effects of ANP (Holtwick, R., Gotthardt, M., Skryabin, B., Steinmetz, M., Potthast, R., Zetsche, B., Hammer, R. E., Herz, J., and Kuhn M. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 7142-7147). The purpose of this study was to clarify mechanisms compensating for the missing vasodilator responses to ANP. In particular, we analyzed the effect of the endothelial, cGMP-mediated vasodilators C-type natriuretic peptide and nitric oxide (NO). In isolated arteries from SMC GC-A KO mice, the vasorelaxing sensitivity to sodium nitroprusside and the endotheliumdependent vasodilator, acetylcholine, was significantly greater than in control mice. There was no difference in responses to C-type natriuretic peptide or to the activator of cGMP-dependent protein kinase I, 8-para-chlorophenylthio-cGMP. The aortic expression of soluble GC (sGC), but not of endothelial NO synthase or cGMP-dependent protein kinase I, was significantly increased in SMC GC-A KO mice. Chronic oral treatment with the NO synthase inhibitor N w -nitro-L-arginine methyl ester increased arterial blood pressure, the effect being significantly enhanced in SMC GC-A KO mice. We conclude that SMC GC-A KO mice exhibit a higher vasodilating sensitivity to NO. This can be attributed to an enhanced expression of sGC, whereas the expression and/or activity levels of downstream cGMP-effector pathways are not involved. Increased vasodilating responsiveness to endothelial NO contributes to compensate for the missing vasodilating effect of ANP in SMC GC-A KO mice.Cyclic GMP-dependent modulation of vascular tone is fundamental to the regulation of blood pressure. The levels of cGMP in vascular smooth muscle cells (SMC) 1 are regulated by the activities of three different guanylyl cyclases (GCs): soluble GC (sGC), the intracellular receptor for endothelial nitric oxide (NO) (1); particulate GC-A, a specific membrane receptor for the cardiac natriuretic peptides, atrial (ANP) and B-type (BNP) natriuretic peptides (2, 3); and particulate GC-B, a specific receptor for the endothelial C-type natriuretic peptide (CNP) (4, 5). Stimulation of either GC results in the conversion of GTP to the intracellular messenger cGMP. Subsequent increases in cellular cGMP modulate the activity of specific cGMP-effector molecules, i.e. cGMP-dependent protein kinase I (PKG I), ultimately leading to decreased cytosolic calcium levels and relaxation of vascular smooth muscle cells (6, 7). Thereby, local factors released by the vascular endothelium (NO and CNP) and circulating hormones (ANP and BNP) cooperate in the cGMP-mediated regulation of vascular tone. In addition, it has been suggested that the vasodilating effect o...

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“…The magnitude of intra-arterial blood pressure elevation in ANP null mice, however, was similar to that in GC-A null mice when fed either a low-salt diet (0.008% NaCI) or a high-salt diet (8% NaCI) [183]. Acute intravenous volume expansion caused a decreased diuretic and natriuretic effect in ANP null mice than in wild-type mice when fed the low-salt diet [183]. Cardiac hypertrophy is reported in ANP null mice fed either a high-salt diet (2% NaCI) or a normal-salt diet (-1% NaCI) [172,184].…”

Section: B Gc-a Transgenic Micementioning

confidence: 69%

“…ANP Null Mice ANP null mice were once reported to exhibit saltdependent blood pressure elevation; blood pressures of ANP null mice measured by the tail-cuff method were 8 mmHg higher than those of wild-type mice on a standard-salt diet (0.5% NaCI), but mean intra-arterial pressures increased to 23 mmHg above those in wild-type mice on a diet of higher salt concentration (2% NaCI) [172]. The magnitude of intra-arterial blood pressure elevation in ANP null mice, however, was similar to that in GC-A null mice when fed either a low-salt diet (0.008% NaCI) or a high-salt diet (8% NaCI) [183]. Acute intravenous volume expansion caused a decreased diuretic and natriuretic effect in ANP null mice than in wild-type mice when fed the low-salt diet [183].…”

Section: B Gc-a Transgenic Micementioning

confidence: 84%

“…The loss of regulation of renin secretion was speculated as a cause of blood pressure elevation in ANP null mice [ 185] . A high-salt diet (8% NaCI), however, markedly increased diuretic and natriuretic effect of acute volume expansion to the same extent in both ANP null and wild-type mice [183]. The reason why the renin-aldosterone profile is different between ANP null and GC-A null mice remains to be elucidated.…”

Section: B Gc-a Transgenic Micementioning

confidence: 97%

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