Title
Angiotensin II-mediated hypertension impairs nitric oxide-induced NKCC2 inhibition in thick ascending limbs
Recommended Citation
Ramseyer VD, Ortiz PA, Carretero OA, Garvin JL. Angiotensin II-mediated hypertension impairs nitric oxide-induced NKCC2 inhibition in thick ascending limbs. Am J Physiol Renal Physiol. Feb 17 2016:ajprenal.00473.02015.
Document Type
Article
Publication Date
4-15-2016
Publication Title
American journal of physiology. Renal physiology
Abstract
In thick ascending limbs (THALs), nitric oxide (NO) decreases NaCl reabsorption via cGMP-mediated inhibition of Na-K-2Cl cotransporter (NKCC2). In angiotensin (ANG II)-induced hypertension, endothelin-1 (ET-1)-induced NO production by THALs is impaired. However, whether this alters NO's natriuretic effects and the mechanisms involved are unknown. In other cell types, ANG II augments phosphodiesterase 5 (PDE5)-mediated cGMP degradation. We hypothesized that NO-mediated inhibition of NKCC2 activity and stimulation of cGMP synthesis are blunted via PDE5 in ANG II-induced hypertension. Sprague-Dawley rats were infused with vehicle or ANG II (200 ng·kg
ANG II: Δ-41 ± 10%). NO increased cGMP by 2.08 ± 0.36 fmol/μg protein in THALs from vehicle-treated rats but only 1.06 ± 0.25 fmol/μg protein in ANG II-hypertensive rats (
Medical Subject Headings
Angiotensin II; Animals; Cyclic CMP; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Endothelin-1; Hypertension; Loop of Henle; Male; Nitric Oxide; Nitric Oxide Donors; Phosphodiesterase 5 Inhibitors; Rats; Rats, Sprague-Dawley; Solute Carrier Family 12, Member 1; Vardenafil Dihydrochloride
PubMed ID
26887831
Volume
310
Issue
8
First Page
748
Last Page
748
