Effects of cardiac hormones on arterial pressure and sodium excretion in NPRA knockout mice.
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 natriuretic peptide (rANP) in 200 microl of saline after the first period (30 mins) and 200 microl of rat atrial extract after the fourth period (120 mins). ANP injection increased urine flow (UF) to 2.7 +/- 0.5 microl/min in the WT versus 1.9 +/- 0.2 in KO. Extract increased UF to 7.9 +/- 1.5 microl/min in WT versus 2.7 +/- 0.4 in KO (P < 0.01). ANP increased sodium excretion (ENa) to 0.47 +/- 0.10 micromoles/min in WT versus 0.27 +/- 0.04 in KO (P < 0.05). Extract increased ENa to 1.44 +/- 0.47 micromoles/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 microl 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.
Dietz
John R
JR
Department of Physiology and Biophysics, University of South Florida, College of Medicine, Tampa, Florida 33612, USA. jdietz@hsc.usf.edu
Landon
Carol S
CS
Nazian
Stanley J
SJ
Vesely
David L
DL
Gower
William R
WR
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D012964:Sodium / Q000652:urine*; D013997:Time Factors; D014020:Tissue Extracts / Q000494:pharmacology
D014020:Tissue Extracts; D009320:Atrial Natriuretic Factor; D012964:Sodium; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A