(769.9) Pulmonary Hypertension Induces Sex Differences in Control of Contracting Rat Skeletal Muscle Oxygen Pressures

Poster Board Number: E600

Kiana Schulze (Kansas State University), Ramona Weber (Kansas State University), Andrew Horn (Kansas State University), Trenton Colburn (Kansas State University), Carl Ade (Kansas State University), David Poole (Kansas State University), Timothy Musch (Kansas State University)

Pulmonary hypertension (PH) is a disease characterized by pulmonary vascular remodeling, cardiac impairments, and skeletal muscle dysfunction. Males and females display different features of the disease, including a higher incidence in females, while males present with greater mortality. Exercise intolerance is a cardinal manifestation of PH, but any potential differences regarding skeletal muscle function during contractions between males and females have not been studied. This investigation tested the hypothesis that sexual dimorphism exists in the oxygen delivery (Q̇O2)-to-oxygen utilization (V̇O2) matching with PH as represented by oxygen partial pressures (PO2) at rest and following the onset of contractions. Considering that females display greater reliance upon nitric oxide (NO) for vascular function and PH decreases NO bioavailability, we hypothesized that PH would attenuate the skeletal muscle PO2 response to a greater extent in females than males.

Methods: Thirty-three Sprague-Dawley rats were randomly assigned to healthy (HC) or PH groups. PH rats (male: n=7; female: n=9) were administered monocrotaline (MCT; 50 mg/kg, i.p.) while HC rats (male: n=9; female: n=8) were given saline. Disease progression was monitored via echocardiography. Phosphorescence quenching determined the O2 partial pressure in the interstitial space (PO2is) in the spinotrapezius muscle at rest and during contractions.

Results: All PH rats displayed criteria for disease including right ventricular (RV) hypertrophy, elevated RV systolic pressure, and pulmonary congestion compared to HC. Indicators of PH severity did not differ between males and females (Pgt;0.05). Females displayed a greater reduction in baseline PO2is in PH versus HC when compared to male counterparts (-29 ± 3% vs. -18 ± 2%; Plt;0.05). No sex differences were present in PO2is kinetics (i.e., tau, amplitude) throughout contractions. However, females with PH reached a lower nadir in PO2is than PH males (4.2 ± 0.3 vs. 7.4 ± 0.4 mmHg; Plt;0.05).

Conclusions: These findings support that Q̇O2-to-V̇O2 matching is impaired in a sex specific manner in skeletal muscle. Individual contributions of O2 delivery and utilization, as well as biochemical analysis of NO in skeletal muscle will be invaluable to elucidating the mechanistic bases for the effects seen herein.

Sustained Momentum for Investigators with Laboratories Established (SMILE) Grant-Kansas State University College of Veterinary Medicine.
NIH Ruth L. Kirschstein National Research Service Award F31HL145981.