757-4 Differential Regulation of Renal Cyclic Nucleotide Phosphodiesterases in Experimental Heart Failure

Autor: Brandt, Roland R., Heinrich, Holger, Chini, Claudia C.S., Aarhus, Lawrence L., Dousa, Thomas P., Burnett, John C.
Zdroj: Journal of the American College of Cardiology; February 1995, Vol. 25 Issue: 2, Number 2 Supplement 1 p235A-235A, 1p
Abstrakt: Thoracic inferior vena caval constriction (TIVCC) is a model of experimentallow cardiac output heart failure (HF) that results in sodium retention and a blunted natriuretic response to atrial natriuretic peptide (ANP). Recognizing that the biological actions of ANP are mediated through guanosine-3’,5’cyclic monophosphate (cGMP) which is metabolized by multiple isozymes of phosphodiesterases (POE), we assessed a role for altered cGMp-POE activity (pmol/mln/mg) In the blunted renal ANP response in HF, Isolated glomeruli and inner medullary collecting duct cells (IMCD) from kidneys of mongrel dogs 8 days following TIVCC (n=4) were compared to control animals (n=6). Total cGMP-POE activity in the presence of 10 I’M calcium (Ca) and 10 μg/ml calmodulin (CaM) was significantly higher in glomeruli from TIVCC (657±81 vs. control 361±31, P<0.05) but not in IMCD (2693±794 vs. control 3371±370, p=NS). From POE isozymes hydrolyzing cGMP in glomeruli, POE-V activity (defined as cGMP-POE in the absence of Ca/CAM) was higher in glomeruli from TIVCC (342±72 vs. control: 154±14, p<0.05), while POE-I activity (defined as total cGMP-POE minus POE-V) and total adenosine 3’,5’-cyclic monophosphate (cAMP) POE activity were not significantly different in glomeruli and IMCD from TIVCC and control dogs.
Databáze: Supplemental Index