Is the Pannexin-1 channel a mechanism underlying hypertension in humans? A translational study of human hypertension

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Background: In preclinical models, the pannexin-1 channel has been shown to be involved in blood pressure regulation through an effect on peripheral vascular resistance. Pannexin-1 releases ATP, which can activate constrictive purinergic receptors on the smooth muscle cells. Pannexin-1 opening is proposed to be mediated by α-adrenergic receptors to potentiate sympathetic constriction. This positions pannexin-1 as a putative pharmacological target in blood pressure regulation in humans. The aim was to provide the first translational evidence for a role of pannexin-1 in essential hypertension in humans by use of an advanced invasive mechanistic approach.

Methods: Middle-aged stage-1 hypertensive (n=13; 135.7±6.4 over 83.7±3.7 mm Hg) and normotensive men (n=12; 117.3±5.7 over 72.2±3.5 mm Hg) were included. Blood pressure and leg vascular resistance were determined during femoral arterial infusion of tyramine (α-adrenergic receptor stimulation), sodium nitroprusside, and acetylcholine. Measurements were made during control conditions and with Pannexin-1 blockade (3000 mg probenecid). Expression of  Pannexin-1, purinergic- and α-adrenergic receptors in skeletal muscle biopsies was determined by Western blot.

Results: The changes in leg vascular resistance in response to tyramine (+289% versus +222%), sodium nitroprusside (-82% versus -78%) and acetylcholine (-40% versus -44%) infusion were not different between the 2 groups (P>0.05) and Pannexin-1 blockade did not alter these variables (P>0.05). Expression of Pannexin-1 and of purinergic- and α-adrenergic receptors was not different between the 2 groups (P>0.05).

Conclusions: Contrary to our hypothesis, the data demonstrate that pannexin-1 does not contribute to the elevated blood pressure in essential hypertension, a finding, which also opposes that reported in preclinical models.

Original languageEnglish
JournalHypertension
Volume79
Issue number5
Pages (from-to)1132-1143
Number of pages12
ISSN0194-911X
DOIs
Publication statusPublished - 2022

    Research areas

  • Faculty of Science - Acetylcholine, Blood pressure, Cardiac output, Probenecid, Tyramine

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