Circulation Research, Vol 74, 747-751, Copyright © 1994 by American Heart Association

ARTICLES

Hemodynamics in transgenic mice with overexpression of atrial natriuretic factor

RW Barbee, BD Perry, RN Re, JP Murgo and LJ Field
Division of Research, Alton Ochsner Medical Institutions, New Orleans, LA 70121.

The circulatory effects associated with lifelong plasma atrial natriuretic factor (ANF) elevation were examined by generating transgenic mice, which constitutively express a fusion gene consisting of the transthyretin promoter and the ANF structural gene. These mice have chronically elevated ANF levels as compared with their nontransgenic siblings. Transgenic animals exhibited immunoreactive ANF levels that were nearly fivefold higher than those measured in nontransgenic littermates. Systemic and regional hemodynamics and blood volumes were explored by using modifications of the reference microsphere and dilution techniques. Mean arterial pressure was reduced by 24 mm Hg, associated with a 27% reduction in total heart weight. This chronic reduction in blood pressure was due to a 21% reduction in total peripheral resistance, whereas cardiac output, stroke volume, and heart rate were not significantly altered, despite a 15% elevation in plasma volume. Transgenic mice displayed reductions of 35%, 33%, 32%, and 19% in muscle, skin, brain, and renal vascular resistance, respectively, whereas coronary and splanchnic resistances were not significantly altered. The findings complement earlier data from chronically infused normotensive mammals and suggest that these mice are an excellent model for investigating the effects of lifelong ANF elevation.

This article has been cited by other articles:

				L. R. Potter, S. Abbey-Hosch, and D. M. Dickey Natriuretic Peptides, Their Receptors, and Cyclic Guanosine Monophosphate-Dependent Signaling Functions Endocr. Rev., February 1, 2006; 27(1): 47 - 72. [Abstract] [Full Text] [PDF]

				D. L. Dries, R. G. Victor, J. E. Rame, R. S. Cooper, X. Wu, X. Zhu, D. Leonard, S.-I. Ho, Q. Wu, W. Post, et al. Corin Gene Minor Allele Defined by 2 Missense Mutations Is Common in Blacks and Associated With High Blood Pressure and Hypertension Circulation, October 18, 2005; 112(16): 2403 - 2410. [Abstract] [Full Text] [PDF]

				J. B. Patel, M. L. Valencik, A. M. Pritchett, J. C. Burnett Jr., J. A. McDonald, and M. M. Redfield Cardiac-specific attenuation of natriuretic peptide A receptor activity accentuates adverse cardiac remodeling and mortality in response to pressure overload Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H777 - H784. [Abstract] [Full Text] [PDF]

				H. C. Thiesson, B. L. Jensen, B. Jespersen, O. B. Schaffalitzky de Muckadell, C. Bistrup, S. Walter, P. D. Ottosen, A. Veje, and O. Skott Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites Am J Physiol Renal Physiol, May 1, 2005; 288(5): F1044 - F1052. [Abstract] [Full Text] [PDF]

				V. Franco, Y.-F. Chen, S. Oparil, J. A. Feng, D. Wang, F. Hage, and G. Perry Atrial Natriuretic Peptide Dose-Dependently Inhibits Pressure Overload-Induced Cardiac Remodeling Hypertension, November 1, 2004; 44(5): 746 - 750. [Abstract] [Full Text] [PDF]

				L. M. Hunt, E. W. Hogeland, M. K. Henry, and S. J. Swoap Hypotension and bradycardia during caloric restriction in mice are independent of salt balance and do not require ANP receptor Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1446 - H1451. [Abstract] [Full Text] [PDF]

				T. Mori, Y.-F. Chen, J. A. Feng, T. Hayashi, S. Oparil, and G. J Perry Volume overload results in exaggerated cardiac hypertrophy in the atrial natriuretic peptide knockout mouse Cardiovasc Res, March 1, 2004; 61(4): 771 - 779. [Abstract] [Full Text] [PDF]

				D. Bernstein Exercise assessment of transgenic models of human cardiovascular disease Physiol Genomics, May 13, 2003; 13(3): 217 - 226. [Abstract] [Full Text] [PDF]

				B. J. A. Janssen and J. F. M. Smits Autonomic control of blood pressure in mice: basic physiology and effects of genetic modification Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1545 - R1564. [Abstract] [Full Text] [PDF]

				J. N. Lorenz A practical guide to evaluating cardiovascular, renal, and pulmonary function in mice Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1565 - R1582. [Abstract] [Full Text] [PDF]

				B. Janssen, J. Debets, P. Leenders, and J. Smits Chronic measurement of cardiac output in conscious mice Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2002; 282(3): R928 - R935. [Abstract] [Full Text] [PDF]

				V. A. Peotta, E. C. Vasquez, and S. S. Meyrelles Cardiovascular Neural Reflexes in L-NAME-Induced Hypertension in Mice Hypertension, September 1, 2001; 38(3): 555 - 559. [Abstract] [Full Text] [PDF]

				T. Suzuki, T. Yamazaki, and Y. Yazaki The role of the natriuretic peptides in the cardiovascular system Cardiovasc Res, August 15, 2001; 51(3): 489 - 494. [Abstract] [Full Text] [PDF]

				B. H. Wang, X.-J. Du, D. J. Autelitano, C. A. Milano, and E. A. Woodcock Adverse effects of constitutively active alpha 1B-adrenergic receptors after pressure overload in mouse hearts Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1079 - H1086. [Abstract] [Full Text] [PDF]

				L. G. MELO, M. E. STEINHELPER, S. C. PANG, Y. TSE, and U. ACKERMANN ANP in regulation of arterial pressure and fluid-electrolyte balance: lessons from genetic mouse models Physiol Genomics, June 29, 2000; 3(1): 45 - 58. [Abstract] [Full Text] [PDF]

				L. G. Melo, S. C. Pang, and U. Ackermann Atrial Natriuretic Peptide: Regulator of Chronic Arterial Blood Pressure Physiology, June 1, 2000; 15(3): 143 - 149. [Abstract] [Full Text] [PDF]

				U. Ackermann and N. Azizi Increased central AT1-receptor activation, not systemic vasopressin, sustains hypertension in ANP knockout mice Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2000; 278(6): R1441 - R1445. [Abstract] [Full Text] [PDF]

				H. C. Champion, D. J. Villnave, A. Tower, P. J. Kadowitz, and A. L. Hyman A novel right-heart catheterization technique for in vivo measurement of vascular responses in lungs of intact mice Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H8 - H15. [Abstract] [Full Text] [PDF]

				L. G. Melo, A. T. Veress, U. Ackermann, and H. Sonnenberg Chronic regulation of arterial blood pressure by ANP: role of endogenous vasoactive endothelial factors Am J Physiol Heart Circ Physiol, November 1, 1998; 275(5): H1826 - H1833. [Abstract] [Full Text] [PDF]

				P. A Doevendans, M. J. Daemen, E. D de Muinck, and J. F Smits Cardiovascular phenotyping in mice Cardiovasc Res, July 1, 1998; 39(1): 34 - 49. [Abstract] [Full Text] [PDF]

				D. L. Mattson Long-term measurement of arterial blood pressure in conscious mice Am J Physiol Regulatory Integrative Comp Physiol, February 1, 1998; 274(2): R564 - R570. [Abstract] [Full Text] [PDF]

				J. Vogel Measurement of cardiac output in small laboratory animals using recordings of blood conductivity Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2520 - H2527. [Abstract] [Full Text] [PDF]

				C.-F. Wu, N. H. Bishopric, and R. E. Pratt Atrial Natriuretic Peptide Induces Apoptosis in Neonatal Rat Cardiac Myocytes J. Biol. Chem., June 6, 1997; 272(23): 14860 - 14866. [Abstract] [Full Text] [PDF]