Pulmonary hypertension impairs vasomotor function in rat diaphragm arterioles

Schulze, Kiana M.; Horn, Andrew G.; Muller-Delp, Judy M.; White, Zachary J.; Hall, Stephanie E.; Medarev, Steven L.; Weber, Ramona E.; Poole, David C.; Musch, Timothy I.; Behnke, Bradley J.

doi:10.1016/j.mvr.2024.104686

Microvascular Research

2024

DOI: 10.1016/j.mvr.2024.104686

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Pulmonary hypertension impairs vasomotor function in rat diaphragm arterioles

Kiana M. Schulze,

Andrew G. Horn,

Judy M. Muller-Delp

et al.

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2024

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Cited by 2 publications

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Skeletal and respiratory muscle blood flow redistribution during submaximal exercise in pulmonary hypertensive rats

Schulze,

Weber,

Horn

et al. 2024

The Journal of Physiology

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Pulmonary hypertension (PH) is a chronic, progressive disease characterized by pulmonary vascular remodelling, dyspnoea and exercise intolerance. Key facets of dyspnoea and exercise intolerance include skeletal and respiratory muscle contractile and metabolic disturbances; however, muscle perfusion during exercise has not been investigated. We hypothesized that diaphragm blood flow () would be increased and locomotory muscle would be decreased during submaximal treadmill running in PH rats compared to healthy controls. Female Sprague–Dawley rats were injected (i.p.) with monocrotaline to induce PH (n = 16), or a vehicle control (n = 15). Disease progression was monitored via echocardiography. When moderate disease severity was confirmed, maximal oxygen uptake () tests were performed. Rats were given >24 h to recover, and then fluorescent microspheres were infused during treadmill running (20 m/min, 10% grade; ∼40–50% maximal speed attained during the test) to determine tissue . In PH rats compared with healthy controls, was lower (84 (7) vs. 67 (11) ml/min/kg; P < 0.001), exercising diaphragm was 35% higher and soleus was 28% lower. Diaphragm was negatively correlated with soleus and in PH rats. Furthermore, there was regional redistribution in the diaphragm in PH compared to healthy rats, which may represent or underlie diaphragmatic weakness in PH. These findings suggest the presence of a pathological respiratory muscle blood flow steal phenomenon in PH and that this may contribute to the exercise intolerance reported in patients. imageKey points Pulmonary hypertension (PH) impairs exercise tolerance, which is associated with skeletal and respiratory muscle dysfunction. Increased work of breathing in PH may augment diaphragm blood flow and lower locomotory muscle blood flow during exercise, hindering exercise tolerance. Our findings demonstrate that respiratory muscle blood flow is increased while the locomotory muscle is decreased in PH compared to healthy rats during exercise, suggesting that blood flow is preferentially redistributed to sustain ventilatory demand. Furthermore, blood flow is regionally redistributed within the diaphragm in PH, which may underlie diaphragm dysfunction. Greater respiratory muscle work at a given workload in PH commands higher respiratory muscle blood flow, impairing locomotory muscle oxygen delivery and compromising exercise tolerance, which may be improved by therapeutics which target the diaphragm vasculature.

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Skeletal and respiratory muscle blood flow redistribution during submaximal exercise in pulmonary hypertensive rats

Schulze,

Weber,

Horn

et al. 2024

The Journal of Physiology

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Effects of aging on diaphragm hyperemia and blood flow distribution in male and female Fischer 344 rats

Horn,

Schulze,

Muller-Delp

et al. 2024

American Journal of Physiology-Regulatory, Integrative and Comp

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Aging is associated with inspiratory muscle dysfunction, however, the impact of aging on diaphragm blood flow (BF) regulation, and whether sex-differences exist, is unknown. We tested the hypotheses in young animals, that diaphragm BF and vascular conductance (VC) would be greater in females and that aging would decrease the diaphragm's ability to increase BF with contractions. Young (4-6 months) and old (22-24 months) Fischer-344 rats were divided into four groups: Young Female (YF, n=7), Young Male (YM, n=8), Old Female (OF, n=9), and Old Male (OM, n=9). Diaphragm BF (ml/min/100g) and VC (ml/mmHg/min/100g) were determined, via fluorescent microspheres, at rest and during 1Hz contractions. In YF versus OF, aging blunted the increase in medial costal diaphragm BF (44 ± 5% vs. 16 ± 12%; P < 0.05) and VC (43 ± 7% vs. 21 ± 12%; P < 0.05). Similarly, in YM versus OM, aging blunted the increase in medial costal diaphragm BF (43 ± 6% vs. 24 ± 12%; P < 0.05) and VC (50 ± 6% vs. 34 ± 10%; P < 0.05). Compared to young, dorsal costal diaphragm BF was increased in OF while crural diaphragm BF was increased in OM ( P < 0.05). Compared to age-matched females, dorsal costal diaphragm BF was lower in YM and OM ( P < 0.05). Aging results in an inability to augment medial costal diaphragm BF and alters regional diaphragm BF distribution in response to muscular contractions. Further, sex differences in regional diaphragm BF are present in young and old animals.

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Pulmonary hypertension impairs vasomotor function in rat diaphragm arterioles

Cited by 2 publications

References 50 publications

Skeletal and respiratory muscle blood flow redistribution during submaximal exercise in pulmonary hypertensive rats

Skeletal and respiratory muscle blood flow redistribution during submaximal exercise in pulmonary hypertensive rats

Effects of aging on diaphragm hyperemia and blood flow distribution in male and female Fischer 344 rats

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