Losartan reduces the vasorelaxant effect of atrial natriuretic peptide on basal tone in aorta

The Ca2+- and receptor-dependencies of the basal tone seen in angiotensin I I (Ang II)-conditioned rabbit thoracic aortic rings were investigated. Ca2-free Krebs significantly and partially reversibly reduced basal tone in ao rtic rings that had recovered from an earlier challenge with Ang II; rings not previously exposed to Ang II were unaffected. The effect of Ca2+-free K rebs was similar to the reduction in basal tone evoked by atrial natriureti c peptide (ANP), but was smaller than that seen with exposure to Ca2+-free Krebs+EGTA+sodium nitroprusside (SNP). Pretreating rings with Ca2+-free Kre bs blocked the vasorelaxant effects of ANP and Ca2+-free Kaebs+EGTA+SNP. Lo sartan, an AT(1) receptor antagonist, significantly attenuated ANP-induced relaxation, but did not otherwise alter basal tension in either unstimulate d or Ang II-conditioned rings. The AT(2) receptor antagonist, PD 123319, ha d no effect. These data suggest that transient exposure to Ang Il induces p rolonged, AT(1)-dependent increases in intracellular free Ca2+ which are an tagonized by ANP.