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Fluid retention in congestive heart failure-the role of natriuretic peptides and arginine vasopressin

University of British Columbia

Fluid retention is associated with congestive heart failure (CHF). The role played by atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and arginine vasopressin (AVP) in CHF is not fully understood. Studies were done in 300days old male normal and cardiomyopathic hamsters with moderate CHF. Their body and heart weights were measured. Blood was collected for ANF measurement. Urine was collected for cAMP, cGMP and creatinine measurement. In vitro cGMP accumulation studies were done in inner medullary duct cells (IMCD) cells upon stimulation by ANF, and in glomeruli upon stimulation by ANF, BNP and CNP. cAMP accumulation studies were done in IMCD cells upon addition of AVP and forskolin. ANF, BNP and CNP radioligand studies were performed in glomerular membrane. Results showed that baseline cGMP/creatinine ratios and the plasma ANF levels were higher in the cardiomyopathic hamsters. The plasma ANF levels correlated with the total heart weight/body weight ratios of the diseased hamsters. The urinary cGMP/creatinine ratios also correlated with the plasma ANF levels. ANF-stimulated cGMP accumulation in glomeruli and IMCD cells of cardiomyopathic hamsters were higher than normal animals. Greater accumulation of cGMP also occurred in cardiomyopathic hamster glomeruli after BNP addition. No increase in cGMP was observed in glomeruli stimulated by CNP in both groups. AVP- and forskolin-stimulated cAMP accumulations in IMCD cells were higher in cardiomyopathic animals. ANF radioligand studies showed that the affinities of the high affinity receptor were similar between the two groups, but the affinity of the low affinity receptors was reduced in cardiomyopathic hamsters. The density of high and low affinity ANF receptors were both increased in cardiomyopathic hamsters. The affinity of BNP high affinity receptor increased significantly. Other changes of BNP receptor properties were similar to that of ANF. CNP radioligand experiments showed no CNP binding in hamster glomeruli. In conclusion, there is activation of the natriuretic peptide system at the hormonal, receptor and second messenger levels in CHF. It is likely that AVP hypersensitivity rather than natriuretic peptide hyposensitivity in kidney is the possible underlying mechanism of fluid retention in CHF.

Thesis/Dissertation

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2008-09-30

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http://hdl.handle.net/2429/2408

Medicine

University of British Columbia

UBCV

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