Histamine Modulation for Low Blood Pressure

Overseen By John R Halliwill, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Oregon

Must not be taking: Antihistamines

Disqualifiers: Cardiovascular disease, Diabetes, Asthma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

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. ^{1 2 3 4 5}

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. ^{2 4 5 6 7}

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. ^{3 4 5 6 7}

Research Team

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.

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

Trial Overview The 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

Group I: Resistance and Aerobic Exercise Experimental Treatment 1 Intervention

Blood and urine collected during recovery from two modalities of exercise

Group II: Heating Experimental Treatment 1 Intervention

Blood and skeletal muscle microdialysate collected during local and/or whole body heating

Group III: Aerobic Exercise and Muscle Perfusion Experimental Treatment 2 Interventions

Muscle perfusion measured during aerobic exercise

Group IV: Aerobic Exercise Experimental Treatment 1 Intervention

Blood and skeletal muscle microdialysate collected during dynamic knee-extension exercise

Who Is Running the Clinical Trial?

University of Oregon

Lead Sponsor

Trials

91

Recruited

46,700+

Findings from Research

A single session of aerobic exercise leads to a drop in blood pressure (postexercise hypotension) and prolonged widening of blood vessels (vasodilatation) in the muscles that were exercised, which is influenced by reduced sympathetic nerve activity and local vasodilator mechanisms.

Recent studies suggest that specific receptors in the brain and histamine receptors in muscles are crucial for these postexercise effects, indicating potential therapeutic avenues for managing conditions like hypertension and diabetes through exercise recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postexercise hypotension and sustained postexercise vasodilatation: what happens after we exercise? Halliwill, JR., Buck, TM., Lacewell, AN., et al.[2022]

In a study of 49 young and healthy individuals (22 Black and 27 Caucasian), it was found that Black participants exhibited elevated diastolic blood pressure (BP) after exercise, unlike Caucasians, indicating different cardiovascular responses to exercise between these groups.

The study suggests that histamine receptors (H1R and H2R) may play a role in these differential responses, as their blockade affected stroke volume differently in Black and Caucasian participants, highlighting potential implications for cardiovascular disease risk in Black individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Post-Exercise Blood Pressure Responses between Blacks and Caucasians. Yan, H., Behun, MA., Cook, MD., et al.[2022]

In a study involving 16 volunteers, taking combined histamine H1/H2-receptor antagonists during exercise led to increased leg blood flow, contrary to the expectation that blocking histamine would reduce it.

The increase in blood flow was observed across various exercise intensities (20% to 80% of peak power) and during prolonged exercise, suggesting that histamine may play a complex role in regulating blood flow during physical activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of histamine-receptor antagonism on leg blood flow during exercise. Ely, MR., Ratchford, SM., La Salle, DT., et al.[2021]

In a study of 20 recreationally active males, those with high-normal blood pressure exhibited an exaggerated blood pressure response to exercise, which was linked to impaired histamine receptor function.

The blockade of histamine H1 and H2 receptors during exercise led to increased mean arterial pressure and decreased total vascular conductance in normotensive individuals, suggesting that histamine plays a role in regulating blood pressure responses during physical activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of combined histamine H1 and H2 receptor blockade on hemodynamic responses to dynamic exercise in males with high-normal blood pressure. Naylor, A., Shariffi, B., Gillum, TL., et al.[2021]

During and after acute aerobic exercise, interstitial histamine levels in skeletal muscle increase, which is crucial for sustaining blood flow to active muscles, with a significant increase of 4.2 ng/ml observed post-exercise.

The increase in histamine is due to both the de novo formation via the enzyme histidine decarboxylase and mast cell degranulation, indicating that exercise triggers a response that enhances muscle recovery and blood flow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mast cell degranulation and de novo histamine formation contribute to sustained postexercise vasodilation in humans. Romero, SA., McCord, JL., Ely, MR., et al.[2018]

In a study of 14 healthy men, histamine was found to lower blood pressure and vascular resistance during submaximal exercise by activating H2 receptors, indicating its role in cardiovascular regulation during physical activity.

The blockade of H2 receptors led to increased blood pressure and cardiac workload during exercise, suggesting that histamine's effects are primarily vascular rather than affecting the heart muscle directly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histamine H2 receptor blockade augments blood pressure responses to acute submaximal exercise in males. Doh, HW., Stebbins, CL., Choi, HM., et al.[2017]

After small muscle-mass dynamic exercise, there is a significant increase in blood flow to the exercised leg, which is mediated by histamine receptors, as shown in a study involving 21 participants.

In contrast, resistance exercise does not lead to sustained vasodilatation, indicating that the mechanisms activating histamine receptors are specific to the type of exercise performed, particularly aerobic activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained postexercise vasodilatation and histamine receptor activation following small muscle-mass exercise in humans. Barrett-O'Keefe, Z., Kaplon, RE., Halliwill, JR.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Postexercise hypotension and sustained postexercise vasodilatation: what happens after we exercise? [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Differential Post-Exercise Blood Pressure Responses between Blacks and Caucasians. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Effect of histamine-receptor antagonism on leg blood flow during exercise. [2021]

4. Canada pubmed.ncbi.nlm.nih.gov

Effects of combined histamine H1 and H2 receptor blockade on hemodynamic responses to dynamic exercise in males with high-normal blood pressure. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Mast cell degranulation and de novo histamine formation contribute to sustained postexercise vasodilation in humans. [2018]

6. Canada pubmed.ncbi.nlm.nih.gov

Histamine H2 receptor blockade augments blood pressure responses to acute submaximal exercise in males. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Sustained postexercise vasodilatation and histamine receptor activation following small muscle-mass exercise in humans. [2022]