Why the study?
The individual contribution of cAMP-generating adenylyl cyclases, particularly soluble adenylyl cyclase (sAC), to endothelial cell Ca2+ signaling remained unclear.
Does sAC inhibition reduce agonist-induced ER-dependent Ca2+ response in endothelial cells?
Population
Human immortalized ECs, primary aortic and cardiac microvascular ECs, primary VSMCs, and ex vivo mouse aortic rings
Comparison
sAC inhibitor KH7 or anti-sAC siRNA vs tmAC inhibitor or control
Design
In vitro and ex vivo preclinical laboratory study
Key result
Inhibition of soluble adenylyl cyclase with KH7 or siRNA prevented ATP-induced intracellular calcium elevation in endothelial cells and reduced phenylephrine-dependent aortic constriction.
Authors
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Hypothesis-generating for sAC in endothelial Ca2+-cAMP signaling; leaves open in vivo validation and clinical relevance.
Does sAC inhibition reduce agonist-induced ER-dependent Ca2+ response in endothelial cells?
Soluble adenylyl cyclase (sAC) regulates agonist-induced ER-dependent calcium responses in endothelial cells, highlighting a potential novel target for hypertension and heart failure.
Mewes et al. (2019) studied this question. sAC-specific inhibitor KH7 or anti-sAC-small interfering RNA vs. Transmembrane AC (tmAC) inhibitor / Control was evaluated on ATP-induced [Ca2+]i elevation and l-phenylephrine-dependent constriction. Inhibition of soluble adenylyl cyclase with KH7 or siRNA prevented ATP-induced intracellular calcium elevation in endothelial cells and reduced phenylephrine-dependent aortic constriction.
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