Histamine Modulation for Low Blood Pressure
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Oregon
Must not be taking: Antihistamines
Disqualifiers: Cardiovascular disease, Diabetes, Asthma, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?
This study is investigating the role of histamine in generating adaptation to exercise
Will I have to stop taking my current medications?
The trial requires that participants are not on any ongoing medical therapy, except for birth control, and do not use over-the-counter or prescription antihistamines.
What data supports the effectiveness of the treatment Exercise, Physical Activity, Workout, Fitness Training for low blood pressure?
Research shows that exercise can lead to a temporary drop in blood pressure after working out, which is linked to increased blood flow in muscles due to histamine (a chemical in the body) activity. This suggests that exercise might help manage blood pressure by affecting how blood vessels behave.12345
Is histamine modulation for low blood pressure safe for humans?
Research shows that blocking histamine receptors during exercise can affect blood pressure and heart function, but these effects vary among individuals. Generally, histamine plays a role in blood flow changes during and after exercise, and while it can cause increased blood pressure in some cases, it is not associated with severe safety concerns in healthy individuals.24567
How does exercise as a treatment for low blood pressure differ from other treatments?
Exercise as a treatment for low blood pressure is unique because it naturally increases blood flow and involves the body's own histamine production, which can enhance blood circulation during and after physical activity. Unlike medications, exercise leverages the body's physiological responses to improve blood pressure regulation without the need for external substances.34567
Research Team
JR
John R Halliwill, PhD
Principal Investigator
University of Oregon
Eligibility Criteria
This trial is for healthy adults aged 18-40 who have not been diagnosed with cardiovascular disease, diabetes, autonomic disorders, or asthma. Participants should not smoke or use nicotine and must not be on any antihistamines or ongoing medical therapy (except birth control). They cannot be pregnant, breastfeeding, planning pregnancy soon, highly active physically, overweight (BMI over 28), non-English speaking, or have high blood pressure.Inclusion Criteria
I am between 18 and 40 years old.
Exclusion Criteria
You have a high level of physical activity based on the International Physical Activity Questionnaire.
I am currently on medication other than birth control.
You are allergic to certain drugs, anesthetics, skin disinfectants, adhesives, or latex.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Exercise Intervention
Participants perform exercise or participate in interventions like heating to study histamine's role in adaptation to exercise
1 hour per session
Multiple sessions (in-person)
Follow-up
Participants are monitored for histamine concentration and metabolites in blood and urine
24 hours
Treatment Details
Interventions
- Exercise (Other)
Trial OverviewThe study examines how histamine helps the body adapt to exercise by comparing the effects of aerobic exercise alone versus combined resistance and aerobic exercise. It also tests the impact of blocking histamine with a drug called alpha-FMH and using common antihistamines after exercising.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: Resistance and Aerobic ExerciseExperimental Treatment1 Intervention
Blood and urine collected during recovery from two modalities of exercise
Group II: HeatingExperimental Treatment1 Intervention
Blood and skeletal muscle microdialysate collected during local and/or whole body heating
Group III: Aerobic Exercise and Muscle PerfusionExperimental Treatment2 Interventions
Muscle perfusion measured during aerobic exercise
Group IV: Aerobic ExerciseExperimental Treatment1 Intervention
Blood and skeletal muscle microdialysate collected during dynamic knee-extension exercise
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of OregonEugene, OR
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Who Is Running the Clinical Trial?
University of Oregon
Lead Sponsor
Trials
91
Patients Recruited
46,700+
References
Postexercise hypotension and sustained postexercise vasodilatation: what happens after we exercise? [2022]A single bout of aerobic exercise produces a postexercise hypotension associated with a sustained postexercise vasodilatation of the previously exercised muscle. Work over the last few years has determined key pathways for the obligatory components of postexercise hypotension and sustained postexercise vasodilatation and points the way to possible benefits that may result from these robust responses. During the exercise recovery period, the combination of centrally mediated decreases in sympathetic nerve activity with a reduced signal transduction from sympathetic nerve activation into vasoconstriction, as well as local vasodilator mechanisms, contributes to the fall in arterial blood pressure seen after exercise. Important findings from recent studies include the recognition that skeletal muscle afferents may play a primary role in postexercise resetting of the baroreflex via discrete receptor changes within the nucleus tractus solitarii and that sustained postexercise vasodilatation of the previously active skeletal muscle is primarily the result of histamine H(1) and H(2) receptor activation. Future research directions include further exploration of the potential benefits of these changes in the longer term adaptations associated with exercise training, as well as investigation of how the recovery from exercise may provide windows of opportunity for targeted interventions in patients with hypertension and diabetes.
Differential Post-Exercise Blood Pressure Responses between Blacks and Caucasians. [2022]Post-exercise hypotension (PEH) is widely observed in Caucasians (CA) and is associated with histamine receptors 1- and 2- (H1R and H2R) mediated post-exercise vasodilation. However, it appears that blacks (BL) may not exhibit PEH following aerobic exercise. Hence, this study sought to determine the extent to which BL develop PEH, and the contribution of histamine receptors to PEH (or lack thereof) in this population. Forty-nine (22 BL, 27 CA) young and healthy subjects completed the study. Subjects were randomly assigned to take either a combined H1R and H2R antagonist (fexofenadine and ranitidine) or a control placebo. Supine blood pressure (BP), cardiac output and peripheral vascular resistance measurements were obtained at baseline, as well as at 30 min, 60 min and 90 min after 45 min of treadmill exercise at 70% heart rate reserve. Exercise increased diastolic BP in young BL but not in CA. Post-exercise diastolic BP was also elevated in BL after exercise with histamine receptor blockade. Moreover, H1R and H2R blockade elicited differential responses in stroke volume between BL and CA at rest, and the difference remained following exercise. Our findings show differential BP responses following exercise in BL and CA, and a potential role of histamine receptors in mediating basal and post-exercise stroke volume in BL. The heightened BP and vascular responses to exercise stimulus is consistent with the greater CVD risk in BL.
Effect of histamine-receptor antagonism on leg blood flow during exercise. [2021]Histamine mediates vasodilation during inflammatory and immune responses, as well as following endurance exercise. During exercise, intramuscular histamine concentration increases, and its production, appears related to exercise intensity and duration. However, whether histamine contributes to exercise hyperemia and promotes exercise blood flow in an intensity- or duration-dependent pattern is unknown. The purpose of this study was to compare leg blood flow across a range of exercise intensities, before and after prolonged exercise, with and without histamine-receptor antagonism. It was hypothesized that combined oral histamine H1/H2-receptor antagonism would decrease leg blood flow, and the effect would be greater at higher intensities and following prolonged exercise. Sixteen (7F, 9M) volunteers performed single-leg knee-extension exercise after consuming either placebo or combined histamine H1/H2-receptor antagonists (Blockade). Exercise consisted of two graded protocols at 20, 40, 60, and 80% of peak power, separated by 60 min of knee-extension exercise at 60% of peak power. Femoral artery blood flow was measured by ultrasonography. Femoral artery blood flow increased with exercise intensity up to 2,660 ± 97 mL/min at 80% of peak power during Placebo (P < 0.05). Blood flow was further elevated with Blockade to 2,836 ± 124 mL/min (P < 0.05) at 80% peak power (9.1 ± 4.8% higher than placebo). These patterns were not affected by prolonged exercise (P = 0.13). On average, femoral blood flow during prolonged exercise was 12.7 ± 2.8% higher with Blockade vs. Placebo (P < 0.05). Contrary to the hypothesis, these results suggest that histamine receptor antagonism during exercise, regardless of intensity or duration, increases leg blood flow measured by ultrasonography.NEW & NOTEWORTHY Leg blood flow during exercise was increased by taking antihistamines, which block the receptors for histamine, a molecule often associated with inflammatory and immune responses. The elevated blood flow occurred over exercise intensities ranging from 20 to 80% of peak capacity and during exercise of 60 min duration. These results suggest that exercise-induced elevations in histamine concentrations are involved in novel, poorly understood, and perhaps complex ways in the exercise response.
Effects of combined histamine H1 and H2 receptor blockade on hemodynamic responses to dynamic exercise in males with high-normal blood pressure. [2021]While postexercise hypotension is associated with histamine H1 and H2 receptor-mediated postexercise vasodilation, effects of histaminergic vasodilation on blood pressure (BP) in response to dynamic exercise are not known. Thus, in 20 recreationally active male participants (10 normotensive and 10 with high-normal BP) we examined the effects of histamine H1 and H2 receptor blockade on cardiac output (CO), mean atrial pressure (MAP), aortic stiffness (AoStiff), and total vascular conductance (TVC) at rest and during progressive cycling exercise. Compared with the normotensive group, MAP, CO, and AoStiff were higher in the high-normal group before and after the blockade at rest, while TVC was similar. At the 40% workload, the blockade significantly increased MAP in both groups, while no difference was found in the TVC. CO was higher in the high-normal group than the normotensive group in both conditions. At the 60% workload, the blockade substantially increased MAP and decreased TVC in the normotensive group, while there were no changes in the high-normal group. A similar CO response pattern was observed at the 60% workload. These findings suggest that the mechanism eliciting an exaggerated BP response to exercise in the high-normal group may be partially due to the inability of histamine receptors. Novelty Males with high-normal BP had an exaggerated BP response to exercise. The overactive BP response is known due to an increase in peripheral vasoconstriction. Increase in peripheral vasoconstriction is partially due to inability of histamine receptors.
Mast cell degranulation and de novo histamine formation contribute to sustained postexercise vasodilation in humans. [2018]In humans, acute aerobic exercise elicits a sustained postexercise vasodilation within previously active skeletal muscle. This response is dependent on activation of histamine H1 and H2 receptors, but the source of intramuscular histamine remains unclear. We tested the hypothesis that interstitial histamine in skeletal muscle would be increased with exercise and would be dependent on de novo formation via the inducible enzyme histidine decarboxylase and/or mast cell degranulation. Subjects performed 1 h of unilateral dynamic knee-extension exercise or sham (seated rest). We measured the interstitial histamine concentration and local blood flow (ethanol washout) via skeletal muscle microdialysis of the vastus lateralis. In some probes, we infused either α-fluoromethylhistidine hydrochloride (α-FMH), a potent inhibitor of histidine decarboxylase, or histamine H1/H2-receptor blockers. We also measured interstitial tryptase concentrations, a biomarker of mast cell degranulation. Compared with preexercise, histamine was increased after exercise by a change (Δ) of 4.2 ± 1.8 ng/ml (P < 0.05), but not when α-FMH was administered (Δ-0.3 ± 1.3 ng/ml, P = 0.9). Likewise, local blood flow after exercise was reduced to preexercise levels by both α-FMH and H1/H2 blockade. In addition, tryptase was elevated during exercise by Δ6.8 ± 1.1 ng/ml (P < 0.05). Taken together, these data suggest that interstitial histamine in skeletal muscle increases with exercise and results from both de novo formation and mast cell degranulation. This suggests that exercise produces an anaphylactoid signal, which affects recovery, and may influence skeletal muscle blood flow during exercise.NEW & NOTEWORTHY Blood flow to previously active skeletal muscle remains elevated following an acute bout of aerobic exercise and is dependent on activation of histamine H1 and H2 receptors. The intramuscular source of histamine that drives this response to exercise has not been identified. Using intramuscular microdialysis in exercising humans, we show both mast cell degranulation and formation of histamine by histidine decarboxylase contributes to the histamine-mediated vasodilation that occurs following a bout of aerobic exercise.
Histamine H2 receptor blockade augments blood pressure responses to acute submaximal exercise in males. [2017]Histamine is a potent vasodilator that has been found to increase during exercise. We tested the hypothesis that histamine would attenuate blood pressure (BP), cardiac output (CO), and vascular resistance responses to short-term, submaximal dynamic exercise during H2 receptor blockade. Fourteen healthy men (20-29 years of age) were studied. Systolic (SBP), diastolic (DBP), and mean arterial (MAP) BP and heart rate (HR) were assessed at rest and during the last minute of 10 min of submaximal cycling exercise (60% of peak oxygen consumption) in the absence and presence of histamine H2 receptor blockade (ranitidine, 300 mg). Stroke volume (SV) (impedance cardiography) and plasma norepinephrine (NE) were measured, and CO, rate × pressure product (RPP), and total peripheral resistance (TPR) were calculated. Plasma levels of histamine were also measured. H2 blockade had no effects on any variables at rest. During exercise, SBP (184 ± 3 mm Hg vs. 166 ± 2 mm Hg), MAP (121 ± 2 mm Hg vs. 112 ± 5 mm Hg), and RPP (25.9 ± 0.8 × 10(3) mm Hg·beats/min vs. 23.5 ± 0.8 × 10(3) mm Hg/beats·min) were greater during blocked conditions (P
Sustained postexercise vasodilatation and histamine receptor activation following small muscle-mass exercise in humans. [2022]A sustained postexercise vasodilatation, which is histamine receptor mediated, has been observed following single bouts of whole-body exercise, but the mechanisms that regulate activation of histamine receptors following exercise are undefined. Exploration of vasodilatation after small muscle-mass dynamic or resistance exercise could provide novel insight into the pathways responsible for histamine receptor activation. We hypothesized that there would be a vasodilatation of the previously exercised limb following small muscle-mass dynamic and resistance exercise, which would be mediated by histamine receptors. We studied men and women before and after single-leg dynamic (n = 9) or resistance knee-extension exercise (n = 12) on control and blockade days (combined oral H(1) and H(2) receptor antagonism with fexofenadine and ranitidine). We measured arterial blood pressure (automated brachial oscillometry) and femoral artery blood flow (Doppler ultrasound). Dynamic exercise elevated leg vascular conductance in the active leg by 27.2 ± 8.4% at 60 min postexercise (P