Abstract
In response to hypoxia and other stress, the sympathetic (adrenergic) nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1) - adrenergic receptor (AR) subtypes (α1A-, α1B-, and α1D-AR). Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH), contractility of middle cerebral arteries (MCA) is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m) and those exposed to LTH (110 days at 3801 m). Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05) in the maximum tension achieved by 10−5 M phenylephrine (PHE). LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05) inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05) α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2)-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.
Highlights
Acute hypoxia leads to a significant increase in cerebral blood flow [1]
The maximum tension achieved in middle cerebral arteries (MCA) by 1025 M PHE was reduced significantly in the long-term hypoxia (LTH) exposed arteries as compared to the normoxic control (Figure 1B)
The present report is an extension of our previous studies on the mechanisms by which the cerebral vasculature acclimatizes to LTH
Summary
Acute hypoxia leads to a significant increase in cerebral blood flow [1]. with successful acclimatization to hypoxia, the cerebral blood flow returns to the values similar to individuals at sea-level [2,3]. Associated changes with the normal acclimatization response include: hypercapnia, polycythemia, high hemoglobin concentration, and angiogenesis. These changes are crucial to maintain normal blood flow normal with adequate tissue oxygenation [4]. Dysregulation of the normal acclimatization responses can lead to acute or chronic mountain sickness, high altitude cerebral edema, chronic migraine headache, and other high altitude-associated disorders [5,6,7,8]. In the LTH animal the distribution of the reduced cardiac output was altered so that blood flow to the brain was maintained at near normal levels [2,3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
