Increased vascular α1-adrenergic receptor sensitivity in older adults with posttraumatic stress disorder

Am J Physiol Regul Integr Comp Physiol. 2020 Dec 1;319(6):R611-R616. doi: 10.1152/ajpregu.00155.2020. Epub 2020 Sep 23.

Abstract

Posttraumatic stress disorder (PTSD) is an independent risk factor for the development of hypertension and cardiovascular disease. Patients with PTSD have heightened blood pressure and sympathetic nervous system reactivity; however, it is unclear if patients with PTSD have exaggerated vasoconstriction in response to sympathetic nerve activation that could also contribute to increased blood pressure reactivity. Therefore, we hypothesized that patients with PTSD have increased sensitivity of vascular α1-adrenergic receptors (α1ARs), the major mediators of vasoconstriction in response to release of norepinephrine at sympathetic nerve terminals. To assess vascular α1AR sensitivity, we measured the degree of venoconstriction in a dorsal hand vein in response to exponentially increasing doses of the selective α1AR agonist, phenylephrine (PE), in 9 patients with PTSD (age = 59 ± 2 yr) and 10 age-matched controls (age = 60 ± 1 yr). Individual dose-response curves were generated to determine the dose of PE that induces 50% of maximal venoconstriction (i.e., PE ED50) reflective of vascular α1AR sensitivity. In support of our hypothesis, PE ED50 values were lower in PTSD compared with controls (245 ± 54 ng/min vs. 1,995 ± 459 ng/min, P = 0.012), indicating increased vascular α1AR sensitivity in PTSD. The PTSD group also had an increase in slope of rise in venoconstriction, indicative of an altered venoconstrictive reactivity to PE compared with controls (19.8% ± 1.2% vs. 15.1% ± 1.2%, P = 0.009). Heightened vascular α1AR sensitivity in PTSD may contribute to augmented vasoconstriction and blood pressure reactivity to sympathoexcitation and to increased cardiovascular disease risk in this patient population.

Keywords: dorsal hand vein technique; linear variable differential transformer; stress disorders; sympathetic nervous system; vascular reactivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists / administration & dosage
  • Age Factors
  • Aging / metabolism*
  • Blood Pressure
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Phenylephrine / administration & dosage
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Signal Transduction
  • Stress Disorders, Post-Traumatic / metabolism*
  • Stress Disorders, Post-Traumatic / physiopathology
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / metabolism*
  • Sympathetic Nervous System / physiopathology
  • Vasoconstriction* / drug effects

Substances

  • Adrenergic alpha-1 Receptor Agonists
  • Receptors, Adrenergic, alpha-1
  • Phenylephrine