Nephron-Specific Disruption of Nitric Oxide Synthase 3 Causes Hypertension and Impaired Salt Excretion

Journal of the American Heart Association
Yang GaoDonald E Kohan

Abstract

In vitro studies suggest that nephron nitric oxide synthase 3 (NOS3) modulates tubule Na+ transport. To assess nephron NOS3 relevance in vivo, knockout (KO) mice with doxycycline-inducible nephron-wide deletion of NOS3 were generated. During 1 week of salt loading, KO mice, as compared with controls, had higher arterial pressure and Na+ retention, a tendency towards reduced plasma renin concentration, and unchanged glomerular filtration rate. Chronic high salt-treated KO mice had modestly decreased total NCC and total SPAK/OSR1 versus controls, however percent phosphorylation of NCC (at T53) and of SPAK/OSR1 was increased. In contrast, total and phosphorylated NKCC2 (at T96/101) were suppressed by 50% each in KO versus control mice after chronic salt intake. In response to an acute salt load, KO mice had delayed urinary Na+ excretion versus controls; this delay was completely abolished by furosemide, partially reduced by hydrochlorothiazide, but not affected by amiloride. After 4 hours of an acute salt load, phosphorylated and total NCC were elevated in KO versus control mice. Acute salt loading did not alter total NKCC2 or SPAK/OSR1 in KO versus control mice but increased the percent phosphorylation of NKCC2 (at T96/101 and S1...Continue Reading

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Citations

Jan 10, 2019·American Journal of Physiology. Renal Physiology·Jayalakshmi LakshmipathiDonald E Kohan
Jul 4, 2019·Current Opinion in Nephrology and Hypertension·Aylin R Rodan
Dec 28, 2019·Journal of the American Heart Association·Anees A Banday, Mustafa F Lokhandwala
Oct 23, 2019·Annual Review of Physiology·Dingguo Zhang, David M Pollock
Apr 18, 2020·Journal of the American Society of Nephrology : JASN·Jayalakshmi LakshmipathiDonald E Kohan
Feb 27, 2021·Frontiers in Physiology·Robert RepettiRajeev Rohatgi
Jun 25, 2021·American Journal of Hypertension·Reham H Soliman, David M Pollock

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