Gonadectomy of adult male rats reduces contractility of isolated cardiac myocytes

Abstract

Sex-related differences in cardiac function have been well documented. The extent to which sex hormones are responsible for these differences is unclear. The current study was designed to determine whether castration and androgen replacement resulted in changes in functional expression of genes encoding the L-type calcium channel and Na/Ca exchanger in isolated rat ventricular myocytes. Sixteen weeks of castration produced a 50% decline in dihydropyridine receptor expression levels and a 16% (P < 0.05) increase in time to peak shortening. Furthermore, cardiac myocytes isolated from castrated animals also displayed an 18% (P < 0.001) increase in time to relengthening and an 80% decrease in Na/Ca exchanger gene expression when compared with intact controls. Testosterone treatment of castrated animals completely reversed these effects. These results provide the first evidence that androgens regulate functional expression of the L-type calcium channel and the Na/Ca exchanger in isolated rat ventricular myocytes and thus may play a role in modulating cardiac performance in males and thereby contribute to the observed gender differences in cardiac function.

Effects of androgens on cardiovascular remodeling

“…Marsh et al (1998) have shown that androgen exerts a hypertrophic effect on cardiac myocytes via a direct AR-mediated pathway, and other studies have also shown that androgens induce cardiac hypertrophy (Malhotra et al 1990, Weinberg et al 1999, Cavasin et al 2003, while castration (Morano et al 1990, Cavasin et al 2003, Li et al 2004) and flutamide (Baltatu et al 2002), an AR antagonist, remarkably reduce cardiac hypertrophy. In addition, androgens modulate male cardiac performance by regulating the functional expression of L-type calcium channels in cardiac myocytes (Golden et al 2003). Li et al (2004) showed that castration mitigated not only cardiac hypertrophy but also cardiac fibrosis in male guanylyl cyclase-A-deficient mice.…”

Regulation of Ryanodine Receptor–Mediated Ca2+ Release in Vas Deferens Smooth Muscle Cells

“…RyR1 expression in skeletal muscle is positively regulated by testosterone (14). In cardiac myocytes, testosterone up-regulates the expression of VDCCs and Na + -Ca 2+ exchanger (15), and lines of evidence for non-genomic effects of testosterone on ion channels in cardiac myocytes have been also well accumulated recently (16). However, direct evidence for the regulation of RyR2 expression by testosterone has not been demonstrated.…”

Variation in expression of calcium-handling proteins is associated with inter-individual differences in mechanical performance of rat (Rattus norvegicus) skeletal muscle

“…The ryanodine receptor interacts with the dihydropyridine receptor during the excitation-contraction coupling process, and acts as the sarcoplasmic reticulum calcium release channel. An increased density of dihydropyridine and ryanodine receptors in muscle is correlated with increased shortening velocity and force in isolated muscle (Kandarian et al, 1992;Golden et al, 2003;Mänttäri and Järvilehto, 2005), and their density is increased following endurance training in trout (Anttila et al, 2008). SERCA is responsible for calcium reuptake from the cytoplasm to the sarcoplasmic reticulum, and its activity can therefore determine muscle relaxation rate (Fleming et al, 1990;Wilson et al, 1998).…”