Neuronal nitric oxide synthase supports Renin release during sodium restriction through inhibition of phosphodiesterase 3

American Journal of Hypertension
Johan SällströmA E G Persson

Abstract

Mice with targeted deletion of neuronal nitric oxide (NO) synthase (nNOS⁻(/)⁻) display inability to increase plasma renin concentration (PRC) in response to sodium restriction. nNOS has a distinct expression at the macula densa (MD), and in the present study, it was tested whether nNOS supports renin release by cyclic guanosine monophosphate (cGMP)-mediated inhibition of cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase 3 (PDE3) in juxtaglomerular (JG) cells. The experiments were performed in conscious nNOS⁻(/)⁻ and wild types after 10 days on a low-sodium diet by acute treatment with the PDE3-inhibitor milrinone, the PDE5 inhibitor zaprinast, or vehicle, using a crossover study protocol. PRC was measured with the antibody-trapping technique and blood pressure with telemetry. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were estimated by measurements of inulin- and para-amino hippuric acid (PAH) clearances, respectively. The basal PRC was reduced in nNOS⁻(/)⁻ compared to the wild types. Administration of milrinone caused a more pronounced PRC increase in nNOS⁻(/)⁻, resulting in normalized renin levels, whereas PDE5 inhibition did not affect PRC in any genotype. The blood pressure was similar in bo...Continue Reading

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Dec 20, 2007·American Journal of Hypertension·Johan SällströmA Erik G Persson
Feb 21, 2009·Advances in Experimental Medicine and Biology·Sara StridhFredrik Palm

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Citations

Oct 20, 2010·American Journal of Hypertension·Armin Kurtz
Jan 13, 2012·American Journal of Hypertension·Armin Kurtz
Dec 13, 2017·Oncotarget·Ines BaroneStefania Catalano
Dec 7, 2013·Endocrine Reviews·Monalisa F AzevedoConstantine A Stratakis
Jun 27, 2012·Pflügers Archiv : European journal of physiology·Ulla G FriisBoye L Jensen
Aug 6, 2019·Frontiers in Pharmacology·Andrea SchrammJens Schlossmann

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