Vascular Reactions of the Diving Reflex in Men and Women Carrying Different ADRA1A Genotypes

Abstract

The diving reflex is an oxygen-saving mechanism which is accompanied by apnea, reflex bradycardia development, peripheral vasoconstriction, spleen erythrocyte release, and selective redistribution of blood flow to the organs most vulnerable to lack of oxygen, such as the brain, heart, and lungs. However, this is a poorly studied form of hypoxia, with a knowledge gap on physiological and biochemical adaptation mechanisms. The reflective sympathetic constriction of the resistive vessels is realized via ADRA1A. It has been shown that ADRA1A SNP (p.Arg347Cys; rs1048101) is associated with changes in tonus in vessel walls. Moreover, the Cys347 allele has been shown to regulate systolic blood pressure. The aim of this work was to evaluate whether the ADRA1A polymorphism affected the pulmonary vascular reactions in men and women in response to the diving reflex. Men (n = 52) and women (n = 50) untrained in diving aged 18 to 25 were recruited into the study. The vascular reactions and blood flow were examined by integrated rheography and rheography of the pulmonary artery. Peripheral blood circulation was registered by plethysmography. The ADRA1A gene polymorphism (p.Arg347Cys; rs1048101) was determined by PCR-RFLP. In both men and women, reflective pulmonary vasodilation did occur in response to the diving reflex, but in women this vasodilation was more pronounced and was accompanied by a higher filling of the lungs with blood.. Additionally, ADRA1A SNP (p.Arg347Cys; rs1048101) is associated with sex. Interestingly, women with the Arg347 allele demonstrated the highest vasodilation of the lung vessels. Therefore, our data may help to indicate women with the most prominent adaptive reactions to the diving reflex. Our data also indicate that women and men with the Cys allele of the ADRA1A gene polymorphism have the highest risk of developing lung hypertension in response to the diving reflex. The diving reflex is an oxygen-saving mechanism which is accompanied by apnea, reflex bradycardia development, peripheral vasoconstriction, spleen erythrocyte release, and selective redistribution of blood flow to the organs most vulnerable to lack of oxygen, such as the brain, heart, and lungs. However, this is a poorly studied form of hypoxia, with a knowledge gap on physiological and biochemical adaptation mechanisms.

Intrinsic diving reflex induces potent antioxidative response by activation of NRF2 signaling

“…8 This is regardless of the fact that DR itself generates an initial hypoxia. 2,3 Animals engaging in more frequent dives exhibit elevated levels of antioxidant enzymes, such as SOD and glutathione reductase, indicating a dose-dependent effect of DR on resistance to hypoxic stress. Additionally, professional breath-hold divers experience decreased post-exercise blood lactic acid build-up, acidosis, and lipid peroxidation, indicating reduced oxidative stress overall.…”

“…The diving reflex (DR) is a powerful endogenous mechanism that enhances mammalian survival under hypoxic/anoxic conditions, [1][2][3] partially by augmenting antioxidant defense responses, although the specific underlying mechanisms remain incompletely elucidated. [4][5][6][7][8][9][10] DR is initiated by a combination of trigeminal sensory afferent activation and apnea, eliciting various physiological responses associated with antioxidative stress (Fig.…”

“…1). [1][2][3] Notably, peripheral vasoconstriction and reflexive apnea, key physiological responses induced by DR, have demonstrated the capability to trigger the activation of nuclear factor-erythroid-2-related factor 2 (NRF2) signaling pathways, resulting in antioxidative stress effects. [11][12][13][14][15][16][17] NRF2, a redox-sensitive transcription factor, plays a pivotal role in the antioxidant response system responsible for maintaining cellular homeostasis.…”