Molecular Hydrogen Modulates the Baroreflex Activity and Reduces the Vascular Adrenoreceptor Sensitivity to Phenylephrine and Lung Inflammation in Rats with Pulmonary Hypertension

Background/Objectives: Molecular hydrogen (H2), a natural antioxidant, can selectively reduce hydroxyl radicals and peroxynitrite without affecting signaling molecules such as H2O2 and NO. In addition, H2 can inhibit the synthesis of inflammatory cytokines. Human and animal studies have shown that the inhalation of H2 has a hypotensive effect. In this context, the aim of the present work was to study the effect of H2 on the baroreflex regulation of blood pressure in rats with experimental monocrotaline-induced pulmonary hypertension (MCT) in vivo and the effects of H2 on the reactivity of isolated rat aorta with MCT pulmonary hypertension to α1-adrenoceptor agonists in vitro. Methods: Experiments were performed on male Wistar rats with MCT pulmonary hypertension; animals were placed in plastic chambers aerated with atmospheric air at a rate of 4 L/min with O2 and CO2 control. Cages with the rats of the MCT-H2 and Control-H2 groups were ventilated with air containing 4% H2 twice daily for 2 h each. The MCT-Air and Control-Air groups breathed only atmospheric air. The duration of the experiment was 21 days. On day 20, blood pressure and heart rate (HR) were measured in awake animals and the baroreflex response to phenylephrine (PE) and nitroprusside (NP) was tested. In in vitro experiments, we studied the effect of adding H2 to the perfusion solution on the responsiveness of isolated aortic preparations from MCT and control rats to the α1-adrenoceptor agonist PE and the vasodilators NP and Acetylcholine. Results: When the effect of H2 on the baroreflex response to NP (4.5 μg/kg) was examined in awake rats, the increase in HR was 73.1 ± 16.7 beats/min in the MCT-Air group and 48.1 ± 10.2 beats/min in the MCT-H2 group (p < 0.01). In the Control-H2 and Control-Air groups, there was a trend towards a lower HR in the Control-H2 group, but the differences were not significant. No differences in HR response to PE administration were found between any of the experimental groups. Experiments on isolated aortic preparations from MCT rats showed that the addition of H2 to the perfusion medium resulted in a 30% reduction in the maximal response to PE compared with the MCT group without hydrogen (p < 0.01), and the potency of PE (EC50) decreased threefold (p < 0.05). There was a decrease in tryptase secretion, indicating an anti-inflammatory effect of H2. Conclusions. The results demonstrate that H2 inhalation was associated with an attenuated heart rate response to nitroprusside-induced hypotension and reduced vascular reactivity to phenylephrine in rats with pulmonary hypertension.