Hypertension
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K+ channels play a fundamental role regulating membrane potential of pulmonary artery (PA) smooth muscle cells and their impairment is a common feature in pulmonary arterial hypertension (PAH). K+ voltage-gated channel subfamily Q (KCNQ1-5) or Kv7 channels and their regulatory subunits subfamily E (KCNE) regulatory subunits are known to regulate vascular tone, but whether Kv7 channel function is impaired in PAH and how this can affect the rationale for targeting Kv7 channels in PAH remains unknown. Here, we have studied the role of Kv7/KCNE subunits in rat PA and their possible alteration in PAH. ⋯ Our data indicate that Kv7 channel function is preserved and KCNE4 is upregulated in PAH. Therefore, compared with other downregulated channels, the contribution of Kv7 channels is increased in PAH resulting in an enhanced sensitivity to Kv7 channel modulators. This study provides insight into the potential usefulness of targeting Kv7 channels in PAH.
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Discovery of ACE2 (angiotensin-converting enzyme 2) revealed that the renin-angiotensin system has 2 counterbalancing arms. ACE2 is a major player in the protective arm, highly expressed in lungs and gut with the ability to mitigate cardiopulmonary diseases such as inflammatory lung disease. ACE2 also exhibits activities involving gut microbiome, nutrition, and as a chaperone stabilizing the neutral amino acid transporter, B0AT1, in gut. ⋯ It illustrates new analyses of the structure of ACE2 that provides better understanding of its actions particularly in lung and gut, shedding of ACE2 by ADAM17 (a disintegrin and metallopeptidase domain 17 protein), and role of TMPRSS2 (transmembrane serine proteases 2) in severe acute respiratory syndrome coronavirus-2 entry into host cells. Cardiopulmonary diseases are associated with decreased ACE2 activity and the mitigation by increasing ACE2 activity along with its therapeutic relevance are addressed. Finally, the potential use of ACE2 as a treatment target in COVID-19, despite its role to allow viral entry into host cells, is suggested.
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The aldosterone/renin ratio (ARR) is currently considered the most reliable approach for case detection of primary aldosteronism (PA). ACE (Angiotensin-converting enzyme) inhibitors are known to raise renin and lower aldosterone levels, thereby causing false-negative ARR results. Because ACE inhibitors lower angiotensin II levels, we hypothesized that the aldosterone/equilibrium angiotensin II (eqAngII) ratio (AA2R) would remain elevated in PA. ⋯ On day 15, 2 patients still demonstrated false-negative ARR_plasma renin activity, one of whom also showed a false-negative ARR_direct renin concentration. No false-negative AA2R results were observed on either day 14 or 15. In conclusion, compared with ARR which can be affected by ACE inhibitors causing false-negative screening results, the AA2R seems to be superior in detecting PA among subjects receiving ACE inhibitors.