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 II (Ang II)-conditioned rabbit thoracic aortic rings were investigated. Ca2+ -free Krebs significantly and partially reversibly reduced basal tone in aortic 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 Krebs was similar to the reduction in basal tone evoked by atrial natriuretic peptide (ANP), but was smaller than that seen with exposure to Ca2+ -free Krebs+EGTA+sodium nitroprusside (SNP). Pretreating rings with Ca2+ free Krebs blocked the vasorelaxant effects of ANP and Ca2+ -free Krebs+EGTA+SNP. Losartan, an AT1 receptor antagonist, significantly attenuated ANP-induced relaxation, but did not otherwise alter basal tension in either unstimulated or Ang II-conditioned rings. The AT2 receptor antagonist, PD 123319, had no effect. These data suggest that transient exposure to Ang II induces prolonged, AT1-dependent increases in intracellular free Ca2+ which are antagonized by ANP.
Peral de Bruno
M
M
Department of Physiology, INSIBIO-Nacional University of Tucumán, Argentina.
Romano
L
L
Coviello
A
A
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007552:Isotonic Solutions / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; D009320:Atrial Natriuretic Factor; D000803:Angiotensin I; D019808:Losartan; D002118:Calcium