Premium
Angiotensin II AT1 and AT2 receptors are differentially dysfunctional to regulate Na‐K‐ATPase Activity in the Proximal Tubules of Spontaneously Hypertensive (SHR) rats.
Author(s) -
Hussain Tahir,
Siddiqui Athar H
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.167
Subject(s) - angiotensin ii receptor type 1 , losartan , medicine , endocrinology , receptor , angiotensin ii , receptor antagonist , agonist , stimulation , chemistry , antagonist , biology
Higher antinatriuretic response to angiotensin II (ang II) is believed to contribute to the pathogenesis of hypertension; however, the mechanism is not understood. We have shown that activation of ang II AT 1 receptors stimulates NKA activity while the activation of AT 2 receptors inhibits the enzyme activity. In the present study, the expression and function of AT 1 and AT 2 receptors to regulate Na, K‐ATPase (NKA) activity were investigated in the isolated proximal tubules (PTs) of SHR and Wistar‐Kyoto rats (12 wk). Western blot revealed that AT 1 receptor expression was increased in the PTs of SHR compared to WKY rats, while the expression of AT 2 receptor was similar in both rat strains. CGP42112A (100 nM), an AT 2 receptor agonist significantly inhibited the NKA activity in the PTs of WKY rats, but did not affect the enzyme activity in SHR. The NKA activity inhibition by CGP was attenuated by the AT 2 receptor antagonist PD123319 (1μM), NO synthase inhibitor, L‐NAME and guanylate cyclase inhibitor ODQ, indicating the involvement of AT 2 receptor via NO/cGMP pathway in the NKA activity inhibition in WKY rats. On the other hand, Ang II in a concentration dependent manner (100 −0.1pM) significantly stimulated the NKA activity in the PTs of the SHR but not in WKY rats. Ang II‐mediated stimulation was attenuated by AT 1 receptor antagonist losartan, suggesting the involvement of AT 1 receptor. We conclude that inability of AT 2 receptor to inhibit NKA and enhanced AT 1 receptor‐mediated stimulation of NKA activity may contribute to increase in the renal sodium retention and the pathogenesis of hypertension in SHR (supported by NIH‐DK61578).