INSTITUTO DE INVESTIGACIONES EN CIENCIAS DE LA SALUD
Unidad Ejecutora - UE
Angiotensin II and Anti Diuretic Hormone Exert Synergistic Effects on Thick Ascending Limb Transport in Spontaneously Hypertensive Rats
GUILLERMO B SILVA; LUIS I. JUNCOS; NESTOR H. GARCIA
Lugar: Basel; Año: 2016
ackground: Sodium reabsorption is increased in the thick ascending limb (TAL) of Henle in several hypertensive models. In this segment, while transport is increased by ADH via cAMP, sodium reabsorption results from Ang II-induced superoxide (O2-) production. Surprisingly, it is unknown whether these mechanisms overlap in hypertension. We hypothesized that Ang II and ADH have accumulative effects on TAL's transport during hypertension. Methods: The effect of ADH/Ang II in TALs from spontaneously hypertensive rats (SHR) on oxygen consumption (QO2), cAMP and O2- was measured. Results: Basal QO2 was 113.3 ± 14.2 nmol O2/min/mg protein. Addition of ADH (1 nM) increased QO2 by 198%. In the presence of ADH, Ang II (1 nM) elicited a QO2 transient response and then rose to 321.5 ± 28.3 (p = 0.003 vs. ADH). These accumulative effects could be due to nitric oxide synthase (NOS) uncoupling, lower Ang II ability to decrease cAMP or increased O2-. We first measured QO2 using a NOS inhibitor. Pretreatment with L-NAME did not block the observed interaction (p = 0.001 Ang II vs. ADH). Also, Ang II blocked the ADH-stimulated cAMP accumulation in TAL of SHRs. In the presence of ADH, Ang II increased O2- production in TALs from SHR by 309% (p = 0.015 vs. basal). The O2- scavenger tempol blocked the Ang II effects on QO2. In the presence of the NADPH oxidase inhibitor apocynin, the accumulative effects of ADH and Ang II were abolished. We conclude that (1) in SHR, Ang II has accumulative effects on ADH-stimulated transport; (2) this effect is mediated by AT1 receptors, and increased O2- production.