Na(+)-ATPase in spontaneous hypertensive rats: possible AT(1) receptor target in the development of hypertension.
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.
Queiroz-Madeira
Eugênio P
EP
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS - Bloco G, 21949-900 Rio de Janeiro, RJ, Brazil.
Lara
Lucienne S
LS
Wengert
Mira
M
Landgraf
Sharon S
SS
Líbano-Soares
Janaína D
JD
Zapata-Sudo
Gisele
G
Sudo
Roberto T
RT
Takiya
Christina M
CM
Gomes-Quintana
Elaine
E
Lopes
Anibal G
AG
Caruso-Neves
Celso
C
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*
D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D019808:Losartan