Sexual dimorphism in the control of skeletal muscle interstitial PO2 of heart failure rats: Effects of dietary nitrate supplementation

Abstract

Sex differences in the mechanisms underlying cardiovascular pathophysiology of O2 transport in heart failure (HF) remain to be explored. In HF, nitric oxide (NO) bioavailability is reduced and contributes to deficits in O2 delivery-to-utilization matching. Females may rely more on NO for cardiovascular control and as such experience greater decrements in HF. We tested the hypotheses that moderate HF induced by myocardial infarction would attenuate the skeletal muscle interstitial PO2 response to contractions (PO2is; determined by O2 delivery-to-utilization matching) compared with healthy controls and females would express greater dysfunction than male counterparts. Furthermore, we hypothesized that 5 days of dietary nitrate supplementation (Nitrate; 1 mmol·kg1·day1) would raise PO2is in HF rats. Forty-two Sprague-Dawley rats were randomly assigned to healthy, HF, or HF Nitrate groups (each n 14; 7 female/7 male). Spinotrapezius PO2is was measured via phosphorescence quenching during electrically induced twitch contractions (180 s; 1 Hz). HF reduced resting PO2is for both sexes compared with healthy controls (P 0.01), and females were lower than males (14 1 vs. 17 2 mmHg) (P 0.05). In HF both sexes expressed reduced PO2is amplitudes following the onset of muscle contractions compared with healthy controls (female: 41 7%, male: 26 12%) (P 0.01). In HF rats, Nitrate elevated resting PO2is to values not different from healthy rats and removed the sex difference. Female HF Nitrate rats expressed greater resting PO2is and amplitudes compared with female HF (P 0.05). In this model of moderate HF, O2 delivery-to-utilization matching in the interstitial space is diminished in a sex-specific manner and dietary nitrate supplementation may serve to offset this reduction in HF rats with greater effects in females. NEW & NOTEWORTHY Interstitial PO2 (PO2is; indicative of O2 delivery-to-utilization matching) determines, in part, O2 flux into skeletal muscle. We show that heart failure (HF) reduces PO2is at rest and during skeletal muscle contractions in rats and this negative effect is amplified for females. However, elevating NO bioavailability with dietary nitrate supplementation increases resting PO2is and alters the dynamic response with greater efficacy in female HF rats, particularly at rest and following the onset of muscle contractions.