None listed
Conditions
Brief summary
High blood pressure (hypertension) affects one in three people, and remarkably ~50% of treated patients remain hypertensive. We need to better understand the mechanisms regulating blood pressure in hypertensive patients if new therapies are to be devised. Current treatments target the heart and arterial resistance, but the ‘forgotten’ venous circulation has been largely neglected. We hypothesize that high levels of sympathetic activity in hypertension result in profound constriction of the veins, and that ameliorating this may be an effective way to help control arterial pressure. Our extensive work in hypertensive animal models indicates that the carotid bodies develop tonicity and heightened reflex sensitivity due to excessive ATP bioavailability acting via purinergic (P2) receptors, which drive sympathetic outflows. We wish to determine whether a non-selective P2 receptor blocker reduces peripheral chemoreflex sensitivity, sympathetic activity, venous tone and blood pressure in humans with hypertension. This project will provide novel mechanistic insights into carotid chemoreflex regulation and the neural control of the venous circulation. Translating insights from our animal models of hypertension into the human setting will lay the groundwork for future studies, potentially leading to a paradigm shift in the future treatment of hypertension.
Interventions
Daily oral pyridoxine supplement (5 mg·kg-1·day-1) will be taken in pill form for 4 weeks. Adherence of intervention will be confirmed with drug tablet return and laboratory tests.
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
-Patients with essential hypertension (At least Stage 2 hypertension; untreated office SBP greater or equal to 140 mmHg or DBP greater or equal to 90 mmHg); -Men and women; -Aged over 18 years; -Body mass index <35 kg/m2
Exclusion criteria
-Significant arrhythmias (e.g., atrial fibrillation, previous VT / significant ventricular ectopy) -Hemodynamically significant valvular heart disease (e.g., stenosis, mechanical valve replacement) -Severe left ventricular systolic dysfunction -Recent acute coronary syndrome (<12 months) (e.g., MI, angioplasty, unstable angina) -Previous coronary artery bypass surgery -Secondary causes of hypertension (e.g., phaeochromocytoma) -Recent stroke/TIA (<12 months) -Current smoker -Body mass index <18 kg/m2. -Current pregnancy -Current user of recreational drugs -Current abuser of alcohol -Inability to fully or appropriately provide consent (e.g., language issue, reading capability) -Underlying medical conditions, which in the opinion of the Investigator place the participant at unacceptably high risk for participating in the study.
Outcome results
None listed