Genetic Determinants of Cardiovascular Reactions in Humans with Different Combinations of Alleles in NOs, ADRB2, BDKRB2 and ACE Genes in Response to the Diving Reflex

The diving reflex (DR) is a set of signaling interconnected reflex respiratory and cardiovascular reactions aimed at quickly adapting to diving, or otherwise, to hypoxia. This effect is achieved through reflexive deceleration of the heart’s rhythm, constriction of peripheral vessels and selective redistribution of blood to those organs which are most vulnerable to hypoxia (the brain and heart). Specificity of DR manifestations is determined by species affiliation among animals. The effectiveness of DR in humans depends on the nature of vegetative and humoral regulation in the cardiovascular system. The aim of this study is to determine whether protective cardiovascular mechanisms when diving vary in people with different polymorphisms genes, which produce factors are involved in the regulation of peripheral vascular tone (NOs, ADRB2, BDKRB2, ACE). 96 volunteers (students; aged 18–24) were examined. These subjects were not adapted to diving. DR was activated by submerging their faces in cold water (12–14°C) under laboratory conditions. ECG records were taken for the resting state, during diving simulation (DS) and after apnea. The blood supply to peripheral vessels was measured indirectly using the pulse wave amplitude (PWA) of the photoplethysmogram (PPG). Vascular tone was calculated from the time of its spread (the pulse transit time, PTT). Blood pressure was recorded. DNA samples from all patients’ blood were isolated using phenol‐chloroform extraction. I/D polymorphism (rs4340) of the ACE gene was analysed using PCR. The results were analysed using Mann‐Whitney nonparametric tests (paired comparisons). According to the results of the study, significant decrease in PWA was found in subjects with C/C (ADRB2; n=56) and 4b4b (NOs; n=45) polymorphisms during DS (p<0.01). In its turn, decline in PWA was less significant in subjects with A/A (ADRB2; n=36), G/G (ADRB2; n=21) alleles (p<0.05). And in subjects with 4b4a (NOs; n=21), 4a4a (NOs; n=3) polymorphisms, PWA decreased is not significant. We suggests that the protective mechanisms in subjects with C/C (ADRB2) and 4b4b (NOs) polymorphisms are better expressed. According to the results of the ACE polymorphism study, significant differences in PTT were found between I/D (n=27) and I/I (n=23) alleles, as well as between with I/I and D/D (n=21) alleles at the control level (CL) and during DS (p<0.01; p<0.05). When BDKRB2 alleles were studied, significant differences in PWA between T/C (n=35) and C/C (n=24) alleles, as well as between T/T (n=13) and C/C alleles were found in all dives and during recovery (p<0.01). In subjects with I/D, T/C (BDKRB2), C/C (ADRB2) and 4b4b polymorphisms, PWA increased in the recovery process when compared with CL (p<0.01). This reflects an increase in blood volume in the peripheral vessels and indicates oxygen debt formed during DS. When diving was simulated, constriction of peripheral vessels was observed in all subjects examined, but its severity had significant individual differences. Studies have shown that the most effective defence mechanisms against hypoxia are those which develop when diving in people with I/D (ACE), T/C (BDKRB2), C/C (ADRB2) и 4b4b (NOs) polymorphisms.