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Is the Pannexin-1 Channel a Mechanism Underlying Hypertension in Humans? a Translational Study of Human Hypertension
- Source :
- Gliemann, L, Tamariz-Ellemann, A, Hansen, C C, Ehlers, T S, Møller, S & Hellsten, Y 2022, ' Is the Pannexin-1 channel a mechanism underlying hypertension in humans? A translational study of human hypertension ', Hypertension, vol. 79, no. 5, pp. 1132-1143 . https://doi.org/10.1161/HYPERTENSIONAHA.121.18549
- Publication Year :
- 2022
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2022.
-
Abstract
- 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.
Details
- ISSN :
- 15244563 and 0194911X
- Volume :
- 79
- Database :
- OpenAIRE
- Journal :
- Hypertension
- Accession number :
- edsair.doi.dedup.....4161d0ed66691fce6b41c467db7371ef
- Full Text :
- https://doi.org/10.1161/hypertensionaha.121.18549