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

Abstract

Using a monocrotaline-induced pulmonary hypertension (MCT) model in male Wistar rats, this study examined the cardiovascular and vascular effects of 4% H2 inhalation administered twice daily for 2 hours over 21 days. In awake animals, the heart rate increase following nitroprusside-induced hypotension was significantly lower in the MCT-H2 group (48.1 ± 10.2 beats/min) compared with the MCT-Air group (73.1 ± 16.7 beats/min; p < 0.01), indicating modulation of baroreflex sensitivity. In isolated aortic preparations from MCT rats, adding H2 to the perfusion medium reduced the maximal contractile response to the α-adrenoceptor agonist phenylephrine by approximately 30% and decreased its potency (EC50) threefold. Vasodilatory responses to nitroprusside and acetylcholine were also assessed. Additionally, reduced tryptase secretion in lung tissue pointed to an anti-inflammatory action of H2. These findings collectively indicate that H2 inhalation attenuates autonomic cardiovascular regulation and peripheral vascular adrenergic reactivity in pulmonary hypertension.

Mechanism

H2 selectively scavenges hydroxyl radicals and peroxynitrite while suppressing inflammatory cytokine synthesis, thereby reducing α-adrenoceptor-mediated vascular contractility and modulating baroreflex-driven heart rate responses in pulmonary hypertension.