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Experimental Biology and Medicine 229:813-818 (2004)
© 2004 Society for Experimental Biology and Medicine


ORIGINAL RESEARCH ARTICLE

Effects of Cardiac Hormones on Arterial Pressure and Sodium Excretion in NPRA Knockout Mice

John R. Dietz*,{dagger},1, Carol S. Landon*,{dagger}, Stanley J. Nazian*,{dagger}, David L. Vesely{dagger},{ddagger} and William R. Gower, Jr.*,{dagger},§

* Departments of Physiology & Biophysics, {dagger} the Cardiac Hormone Center, {ddagger} Department of Internal Medicine, and § Departments of Biochemistry & Molecular Biology, University of South Florida, Tampa, Florida 33612

To whom requests for reprints should be addressed at 1 Department of Physiology and Biophysics, University of South Florida, College of Medicine, Box 8, Tampa, FL 33612. E-mail: jdietz{at}hsc.usf.edu

These studies were designed to determine if the atria contains natriuretic substances that act through a non–natriuretic peptide type A (NPRA) receptor mechanism. C57BL/6 mice, either wild-type NPRA++ (WT) or NPRA –– knockout (KO), were anesthetized with pentobarbital. Catheters were placed in the trachea, carotid artery, jugular vein, and bladder. Urine was collected for six 30-min periods. Both groups received an iv injection of 100 ng of rat atrial natriuetic peptide (rANP) in 200 µl of saline after the first period (30 mins) and 200 µl of rat atrial extract after the fourth period (120 mins). ANP injection increased urine flow (UF) to 2.7 ± 0.5 µl/min in the WT versus 1.9 ± 0.2 in KO. Extract increased UF to 7.9 ± 1.5 µl/min in WT versus 2.7 ± 0.4 in KO (P < 0.01). ANP increased sodium excretion (ENa) to 0.47 ± 0.10 µmoles/min in WT versus 0.27 ± 0.04 in KO (P < 0.05). Extract increased ENa to 1.44 ± 0.47 µmoles/min in WT versus 0.26 ± 0.06 in KO (P < 0.05). Extract decreased mean arterial pressure (MAP) to 62 ± 3 mm Hg in the WT versus 81 ± 5 in KO (P < 0.01). ENa and MAP responses to extract in KO were not different from responses to 200 µl of saline. A constant 150-min infusion of rat atrial extract increased urine flow by 3-fold and ENa by 5-fold (both P < 0.05) in the WT mice but had no significant effect in the KO mice. Thus, acute renal and MAP responses to atrial extracts require the NPRA receptor.

Key Words: ANP • atrial extracts • sodium excretion • furosemide







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