Histamine, mast cell tryptase and post-exercise hypotension in healthy and collapsed marathon runners.

PURPOSE: Heat stress exacerbates post-exercise hypotension (PEH) and cardiovascular disturbances from elevated body temperature may contribute to exertion-related incapacity. Mast cell degranulation and muscle mass are possible modifiers, though these hypotheses lack practical evidence. This study had three aims: (1) to characterise pre-post-responses in histamine and mast cell tryptase (MCT), (2) to investigate relationships between whole body muscle mass (WBMM) and changes in blood pressure post-marathon, (3) to identify any differences in incapacitated runners. METHODS: 24 recreational runners were recruited and successfully completed the 2019 Brighton Marathon (COMPLETION). WBMM was measured at baseline. A further eight participants were recruited from incapacitated runners (COLLAPSE). Histamine, MCT, blood pressure, heart rate, body temperature and echocardiographic measures were taken before and after exercise (COMPLETION) and upon incapacitation (COLLAPSE). RESULTS: In completion, MCT increased by nearly 50% from baseline (p = 0.0049), whereas histamine and body temperature did not vary (p > 0.946). Systolic (SBP), diastolic (DBP) and mean (MAP) arterial blood pressures and systemic vascular resistance (SVR) declined (p < 0.019). WBMM negatively correlated with Δ SBP (r = - 0.43, p = 0.046). For collapse versus completion, there were significant elevations in MCT (1.77 ± 0.25 µg/L vs 1.18 ± 0.43 µg/L, p = 0.001) and body temperature (39.8 ± 1.3 °C vs 36.2 ± 0.8 °C, p < 0.0001) with a non-significant rise in histamine (9.6 ± 17.9 µg/L vs 13.7 ± 33.9 µg/L, p = 0.107) and significantly lower MAP, DBP and SVR (p < 0.033). CONCLUSION: These data support the hypothesis that mast cell degranulation is a vasodilatory mechanism underlying PEH and exercise associated collapse. The magnitude of PEH is inversely proportional to the muscle mass and enhanced by concomitant body heating.

Post-exercise hypotension and skeletal muscle oxygenation is regulated by nitrate-reducing activity of oral bacteria.

Post-exercise hypotension (PEH) is a common physiological phenomenon leading to lower blood pressure after acute exercise, but it is not fully understood how this intriguing response occurs. This study investigated whether the nitrate-reducing activity of oral bacteria is a key mechanism to trigger PEH. Following a randomized, double blind and crossover design, twenty-three healthy individuals (15 males/8 females) completed two treadmill trials at moderate intensity. After exercise, participants rinsed their mouth with antibacterial mouthwash to inhibit the activity of oral bacteria or a placebo mouthwash. Blood pressure was measured before, 1h and 2 h after exercise. The microvascular response to a reactive hyperaemia test, as well as blood and salivary samples were taken before and 2 h after exercise to analyse nitrate and nitrite concentrations and the oral microbiome. As expected, systolic blood pressure (SBP) was lower (1 h: -5.2 ±â€¯1.0 mmHg; P < 0.001); 2 h: -3.8 ±â€¯1.1 mmHg, P = 0.005) after exercise compared to baseline in the placebo condition. This was accompanied by an increase of circulatory nitrite 2 h after exercise (2h: 100 ±â€¯13 nM) compared to baseline (59 ±â€¯9 nM; P = 0.013). Additionally, an increase in the peak of the tissue oxygenation index (TOI) during the reactive hyperaemia response was observed after exercise (86.1 ±â€¯0.6%) compared to baseline levels (84.8 ±â€¯0.5%; P = 0.010) in the placebo condition. On the other hand, the SBP-lowering effect of exercise was attenuated by 61% at 1 h in the recovery period, and it was fully attenuated 2 h after exercise with antibacterial mouthwash. This was associated with a lack of changes in circulatory nitrite (P > 0.05), and impaired microvascular response (peak TOI baseline: 85.1 ±â€¯3.1%; peak TOI post-exercise: 84.6 ±â€¯3.2%; P > 0.05). Diversity of oral bacteria did not change after exercise in any treatment. These findings show that nitrite synthesis by oral commensal bacteria is a key mechanism to induce the vascular response to exercise over the first period of recovery thereby promoting lower blood pressure and greater muscle oxygenation.

Exaggerated post exercise hypotension following concentric but not eccentric resistance exercise: Implications for metabolism.

Post exercise hypotension (PEH) is primarily attributed to post-exercise vasodilation via central and peripheral mechanisms. However, the specific contribution of metabolic cost during exercise, independent of force production, is less clear. This study aimed to use isolated concentric and eccentric exercise to examine the role of metabolic activity in eliciting PEH, independent of total work. Twelve participants (6 male) completed upper and lower body concentric (CONC), eccentric (ECC), and traditional (TRAD) exercise sessions matched for work (3 × 10 in TRAD and 3 × 20 in CONC and ECC; all at 65% 1RM). Blood pressure was collected at baseline and every 15 min after exercise for 120 min. Brachial blood flow and vascular conductance were also assessed at baseline, immediately after exercise, and every 30 min after exercise. ⩒O2 was lower during ECC compared to CONC and TRAD (-2.7 mL/Kg/min ± 0.4 and -2.2 mL/Kg/min ± 0.4, respectively p < 0.001). CONC augmented the PEH response (Peak ΔMAP -3.3 mmHg ± 0.9 [mean ± SE], p = 0.006) through 75 min of recovery and ECC elicited a post-exercise hypertensive response through 120 min of recovery (Peak ΔMAP +4.5 mmHg ± 0.8, p < 0.001). CONC and TRAD elicited greater increases in brachial blood flow post exercise than ECC (Peak Δ brachial flow +190.4 mL/min ± 32.3, +202.3 mL/min ± 39.2, and 69.6 mL/min ± 19.8, respectively, p ≤ 0.005), while conductance increased immediately post exercise in all conditions and then decreased throughout recovery following ECC (-32.9 mL/min/mmHg ± 9.3, p = 0.005). These data suggest that more metabolically demanding concentric exercise augments PEH compared to work-matched eccentric exercise.

Deep-targeted exon sequencing reveals renal polymorphisms associate with postexercise hypotension among African Americans.

We found variants from the Angiotensinogen-Converting Enzyme (ACE), Angiotensin Type 1 Receptor (AGTR1), Aldosterone Synthase (CYP11B2), and Adducin (ADD1) genes exhibited intensity-dependent associations with the ambulatory blood pressure (BP) response following acute exercise, or postexercise hypotension (PEH). In a validation cohort, we sequenced exons from these genes for their associations with PEH Obese (30.9 ± 3.6 kg m-2) adults (n = 23; 61% African Americans [AF], 39% Caucasian) 42.0 ± 9.8 years with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) completed three random experiments: bouts of vigorous and moderate intensity cycling and control. Subjects wore an ambulatory BP monitor for 19 h. We performed deep-targeted exon sequencing using the Illumina TruSeq Custom Amplicon kit. Variant genotypes were coded as number of minor alleles (#MA) and selected for further statistical analysis based upon Bonferonni or Benjamini-Yekutieli multiple testing corrected p-values under time adjusted linear models for 19 hourly BP measurements per subject. After vigorous intensity over 19 h among ACE, AGTR1, CYP11B2, and ADD1 variants passing multiple testing thresholds, as the #MA increased, systolic (SBP) and/or diastolic BP decreased 12 mmHg (P = 4.5E-05) to 30 mmHg (P = 6.4E-04) among AF only. In contrast, after moderate intensity over 19 h among ACE and CYP11B2 variants passing multiple testing thresholds, as the #MA increased, SBP increased 21 mmHg (P = 8.0E-04) to 22 mmHg (P = 8.2E-04) among AF only. In this replication study, ACE, AGTR1, CYP11B2, and ADD1 variants exhibited associations with PEH after vigorous, but not moderate intensity exercise among AF only. Renal variants should be explored further with a multi-level "omics" approach for associations with PEH among a large, ethnically diverse sample of adults with hypertension.