title: Na(+)-ATPase in spontaneous hypertensive rats: possible AT(1) receptor target in the development of hypertension.
abstract: Clinical and experimental data show an increase in sodium reabsorption on the proximal tubule (PT) in essential hypertension. It is well known that there is a link between essential hypertension and renal angiotensin II (Ang II). The present study was designed to examine ouabain-insensitive Na(+)-ATPase activity and its regulation by Ang II in spontaneously hypertensive rats (SHR). We observed that Na(+)-ATPase activity was enhanced in 14-week-old but not in 6-week-old SHR. The addition of Ang II from 10(-12) to 10(-6) mol/L decreased the enzyme activity in SHR to a level similar to that obtained in WKY. The Ang II inhibitory effect was completely reversed by a specific antagonist of AT(2) receptor, PD123319 (10(-8) mol/L) indicating that a system leading to activation of the enzyme in SHR is inhibited by AT(2)-mediated Ang II. Treatment of SHR with losartan for 10 weeks (weeks 4-14) prevents the increase in Na(+)-ATPase activity observed in 14-week-old SHR. These results indicate a correlation between AT(1) receptor activation in SHR and increased ouabain-insensitive Na(+)-ATPase activity. Our results open new possibilities towards our understanding of the pathophysiological mechanisms involved in the increased sodium reabsorption in PT found in essential hypertension.
authors: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS - Bloco G, 21949-900 Rio de Janeiro, RJ, Brazil.
authors: Eugênio P
authors: EP
authors: Queiroz-Madeira
authors: Lucienne S
authors: LS
authors: Lara
authors: Mira
authors: M
authors: Wengert
authors: Sharon S
authors: SS
authors: Landgraf
authors: Janaína D
authors: JD
authors: Líbano-Soares
authors: Gisele
authors: G
authors: Zapata-Sudo
authors: Roberto T
authors: RT
authors: Sudo
authors: Christina M
authors: CM
authors: Takiya
authors: Elaine
authors: E
authors: Gomes-Quintana
authors: Anibal G
authors: AG
authors: Lopes
authors: Celso
authors: C
authors: Caruso-Neves
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D006973:Hypertension / Q000201:enzymology* / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007700:Kinetics; D019808:Losartan / Q000494:pharmacology; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D019808:Losartan