Effect of Gender Status on NT-Prohormone Brain Natriuretic Peptide Levels in Dogs
Natriuretic peptides, hormones secreted in response to myocardial stretching and hypoxia, are becoming an increasingly important tools in identifying and characterizing cardiac disease. Amino-terminal prohormone brain natriuretic peptide (NT-proBNP) is increased in dogs with a variety of cardiac diseases including chronic myxomatous valve degeneration, dilated cardiomyopathy, and congestive heart failure. Both age and renal dysfunction have been associated with increased NT-proBNP levels in humans. Recently, reports in the human literature indicate that gender related differences in sex hormones also affects NT-proBNP levels. We hypothesized that these gender-mediated differences occur in dogs as well, with testosterone being inversely related and estradiol having little if any correlation with NT-proBNP.
Nine healthy intact adult dogs (6 males, 3 females) presenting for a routine spay or neuter were recruited into this study. All dogs received a complete physical examination, echocardiogram, and BUN/creatinine prior to surgery. Samples for NT-proBNP and sex hormone assays were obtained prior to neutering and at recheck examination 8 to 25 days post-operatively. NT-proBNP assay was performed using a sandwich enzyme immunoassay by a commercial laboratory (Veterinary Diagnostics Institute). Sex hormones were measured in-house using a radioimmunoassay kit. The minimum sensitivity of the testosterone assay was 0.04 ng/ml, and estradiol was 8 pg/ml.
The NT-proBNP concentrations were as follows (mean±SD pmol/L): intact males (IM) 302.0±73.1, castrated males (CM) 412.0±102.9, intact females (IF) 380.7±153.1, and spayed females (SF) 475.7±106.0. The data was analyzed using a one-way ANOVA and post-hoc Tukey test; p<0.05 was considered significant. There was no significant difference between males and females at baseline (p=0.13), or post-surgery (p=0.41). All subjects showed a significant increase in NT-proBNP levels post-surgery (P=0.012). There was a significant increase in NT-proBNP in CM vs. IM (p=0.04), but not in SF vs. IF (p=0.08).
Testosterone (T, ng/ml) and estradiol (E2, pg/ml) results were as follows (mean±SD): IM-T 2.92±1.8, CM-T < 0.04. IM-E2 8.29±4.0, CM-E2 1.7±2.6. IF-T and SF-T < 0.04. IF-E2 14.49±5.7, SF-E2 4.5±4.2. There were significant reductions in T (p=0.02) and E2 (p=0.001) levels following surgery. Linear regression analysis of pre- and post-surgical sex hormone levels and NT-proBNP failed to show any correlations.
Preliminary results of this study do not support our initial hypothesis; however, this may be due to the small sample size, particularly from females. Alternatively, the increase in NT-proBNP may be related to a surgical or anesthetic effect. Sample collection is on-going and future sampling will include post-surgical echocardiograms, and renal bloodwork.