Premium
Angiotensin II Represses Guanylyl Cyclase/Natriuretic Peptide Receptor‐A Gene Expression and Receptor Signaling and Function
Author(s) -
Arise Kiran K.,
Kumar Prerna,
Samivel Ramachandran,
Zhao Hanqing,
Lindsey Sarah,
Pandey Kailash N.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02216
Subject(s) - npr1 , atrial natriuretic peptide , npr2 , medicine , endocrinology , angiotensin ii , natriuretic peptide , receptor , chemistry , biology , heart failure
Atrial and brain natriuretic peptides (ANP and BNP) bind to guanylyl‐cyclase/natriuretic peptide receptor‐A (GC‐A/NPRA) and regulate sodium excretion, water balance, vasorelaxation, and steroidogenesis; all directed to combat hypertension. ANP acting through NPRA lowers blood pressure and blood volume and protects the heart and vascular disorders and end‐organ damage. The two vasoactive hormones, angiotensin II (ANG II; vasoconstrictive) and atrial natriuretic peptide (ANP; vasodilatory) antagonize the biological actions of each other. The objective of the present study was to examine whether ANG II plays critical roles in the transcriptional repression of Npr1 (encoding for NPRA) and receptor function. To delineate the mechanisms of ANG II‐mediated repression of Npr1 transcription and function, we performed the promoter deletional analyses, which showed that region −1182/−914 base pairs upstream from the transcription start site of the Npr1 promoter contains cis‐acting elements for ANG II‐regulated repression of Npr1 . ANG II significantly decreased the levels of NPRA mRNA (60%), NPRA protein (52%), and intracellular accumulation cGMP (65%) in cultured mesangial cells and attenuated ANP‐mediated relaxation of aortic rings ex vivo . The results showed that transcription factors, CREB and HSF‐4a facilitated the ANG II‐mediated repressive effects on Npr1 transcription and receptor function. The current findings suggest that ANG II‐mediated repressive mechanisms of Npr1 transcription and receptor function may provide new molecular targets for the treatment and prevention of hypertension and renal and vascular disorders. Support or Funding Information This work was supported by NIH grant HL062147