Sex Differences in Sympathetic Vascular Reactivity at High Altitude
Condition: Vasodilation; Vasoconstriction
Study type: Interventional

Summary: 
      This study aims to investigate sex differences in blood pressure control associated with
      exposure to acute hypoxia (low oxygen), and short term acclimatization to hypoxia at high
      altitude.
    

Detailed description: 
      About 200 million people worldwide live at high altitudes and millions of others travel to
      high altitude every year for work or pleasure. At high altitude participants are exposed to a
      lower than normal level of oxygen, also known as hypoxia. This causes stress to the human
      body, which will adapt in order to maintain adequate oxygen delivery to its tissues. One of
      these adaptations is an increase in activity of participants' sympathetic nervous system
      ("fight or flight" response). Sympathetic nerve activity affects the size of participants'
      blood vessels, which in turn will affect blood pressure. Men and women regulate their blood
      pressure in different ways; for example, women tend to have lower blood pressure and
      sympathetic nerve activity than men. Women also appear to have less constriction of their
      blood vessels in response to stress. This may be in part because estrogen causes blood
      vessels to dilate. It may also be due to differences in the receptors which are activated by
      the sympathetic nervous system. These receptors are called alpha and beta receptors and
      respond to sympathetic nerve activity in opposite directions. Women represent 50% of the
      population living at and travelling to high altitude, therefore, it is important to
      understand the differences in how men and women respond to low oxygen.

      The main purpose of this study is to examine the differences between men and women in the
      sympathetic nervous system control of blood vessels during exposure to low oxygen. To study
      this question, the investigators will test how blood vessels respond to stressors in both men
      and women. Participants will be recruited at the Canadian sites, and the investigators will
      test them while they breathe low oxygen for a short amount of time at low altitude. The
      investigators will also perform assessments on the same participants during a two week stay
      at high altitude at White Mountain, CA, which is at an altitude of 3,800m. These data will
      have implications in the basic understanding of differences between male and female
      physiology. Specifically, to males and females living or travelling to high altitude.
    

Intervention name(s): Sodium Nitroprusside; Phenylephrine Hydrochloride; Phenylephrine Hydrochloride; Norepinephrine; Isometric Handgrip and Post-Exercise Circulatory Occlusion; Rhythmic Handgrip; Cold Pressor Test; Propranolol Hydrochloride; Phentolamine Mesylate
Intervention type(s): Drug; Drug; Drug; Drug; Other; Other; Other; Drug; Drug
Intervention description(s): A bolus injection of sodium nitroprusside will be given to lower blood pressure and evaluate baroreflex function.; A bolus injection of phenylephrine will be given to raise blood pressure and evaluate baroreflex function immediately following the sodium nitroprusside infusion.; Investigators will give three incremental doses via brachial artery catheter to observe α1-adrenoreceptor mediated vasoconstriction. This will occur three times throughout the protocol.; Investigators will give three incremental doses via brachial artery catheter to observe adrenoreceptor activation. This will occur three times throughout the protocol.; Participants will perform 2 minutes of isometric handgrip at 30% maximal voluntary contraction followed by 2 minutes of post-exercise circulatory occlusion to assess the reactivity of the blood vessels to exercise and the metaboreflex.; Participants will perform 3 minutes of rhythmic handgrip at 25% maximal voluntary contraction to assess the reactivity of blood vessels to dynamic exercise.; Standardized sympathetic stressor involving submersion of the hand in ice-cold water for 3-minutes, aiming to elicit endogenous neurotransmitter release and blood pressure increases.; Local infusion via brachial artery catheterization will occur continuously for the remainder of the study. Propranolol is a beta-adrenergic antagonist and will allow investigation of the role of beta receptors in responses to various stressors. The above phenylephrine, norepinephrine, isometric handgrip, post-exercise circulatory occlusion, and rhythmic handgrip protocols will be repeated under propranolol infusion.; Local infusion via brachial artery catheterization will occur continuously for the remainder of the study. Phentolamine is an alpha-adrenergic antagonist and will allow investigation the role of alpha receptors in responses to various stressors. It will be continuously infused with propranolol. The above phenylephrine, norepinephrine, isometric handgrip, post-exercise circulatory occlusion, and rhythmic handgrip protocols will be repeated under propranolol infusion.
Other intervention name(s): Neo-Synephrine
Intervention MeSH terms: Propranolol; Nitroprusside; Phentolamine; Phenylephrine; Oxymetazoline; Norepinephrine; Synephrine
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Intervention model description: Participants will partake in both arms of the study, which include: 1) low altitude and 2) high altitude assessments.
Masking: None (Open Label)
Primary purpose: Basic Science