Impact of castration on changes in left ventricular diastolic pressure-volume relations induced by chronic adrenergic stimulation in rats
Journal of Cardiovascular Pharmacology
School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Rd, Parktown, Johannesburg 2193, South Africa
A reduced testosterone concentration characterizes heart failure and independently predicts outcomes. Although testosterone replacement therapy may have non cardiac-related therapeutic benefits in heart failure, whether reduced testosterone concentrations protect against adverse left ventricular remodeling (LV dilatation) is uncertain. We therefore evaluated whether surgical castration modifies LV dilatation after 6 months of daily injections of the β-adrenergic receptor (AR) agonist, isoproterenol (ISO) (0.015 mg·kg·d), to rats. The extent of LV dilatation and LV systolic chamber dysfunction were determined using both echocardiography and isolated perfused heart procedures. The extent of LV dilatation was determined from LV diastolic pressure-volume (P-V) relationships. As compared with the saline vehicle-treated group, after 6 months of β-AR activation in sham-castrated rats, a marked right shift in the LV diastolic P-V relationship was noted with an increased LV volume intercept at 0 mm Hg diastolic pressure (LV V0 in milliliters) (ISO = 0.38 ± 0.02, saline vehicle = 0.30 ± 0.02, P < 0.05). However, chronic β-AR activation did not alter LV systolic chamber function either in vivo (LV endocardial fractional shortening, echocardiography) or ex vivo (LV end systolic elastance). Although castration decreased body weight, castration failed to modify the impact of ISO on the LV diastolic P-V relationships or the LV volume intercept at 0 mm Hg diastolic pressure (LV V0 in milliliters) (castration ISO = 0.35 ± 0.02, castration saline vehicle = 0.27 ± 0.03, P < 0.05). In conclusion, castration does not influence the extent of LV dilatation induced by chronic adrenergic activation in an animal model, where adverse LV remodeling precedes LV systolic chamber dysfunction. Copyright © 2014 by Lippincott Williams & Wilkins.
isoprenaline; sodium chloride; beta adrenergic receptor stimulating agent; adrenergic stimulation; animal experiment; animal model; article; body weight; castration; compliance (physical); controlled study; diastolic blood pressure; echocardiography; endocardium; ex vivo study; heart dilatation; heart left ventricle diastolic pressure; heart left ventricle diastolic volume; heart left ventricle endsystolic volume; heart ventricle remodeling; heart volume; in vivo study; left ventricular systolic dysfunction; male; nonhuman; priority journal; rat; weight reduction; animal; blood pressure; chemically induced; drug effects; heart left ventricle function; orchiectomy; pathophysiology; physiology; Sprague Dawley rat; toxicity; Adrenergic beta-Agonists; Animals; Blood Pressure; Male; Orchiectomy; Rats; Rats, Sprague-Dawley; Ventricular Dysfunction, Left; Ventricular Remodeling