Tonic tone in arteries exposed continuously to angiotensin II in vitro

We evaluated long-term actions of angiotensin II (ATII) on arterial smooth muscle. In isolated sympathectomized renal artery segments that had been denuded of endothelium, isometric force was recorded during 3 days of incubation in nutrient medium with and without 1 microM ATII. The peptide induced, after an acute transient contraction and a latency of at least 12 hr, a slowly developing tonic increase in wall tension. This chronic effect was not influenced by indomethacin but could be reversed by sodium-nitroprusside. In vessels that had been chronically exposed to ATII, acute contractile responses to high potassium, serotonin and ATII were not altered. Also effects on agonist-induced tone of removal and readministration of extracellular potassium were not modified. Relaxing responses after exposure to NH4Cl were attenuated. During continuous exposure of isolated arteries to ATII, release of a stable contractile factor could not be detected, nuclear incorporation of the thymidine analog 5-bromo-2'-deoxyuridine was not stimulated, but the media cross-sectional area was significantly increased. These observations indicate that ATII induces in arterial smooth muscle, besides its well known acute contractile effect and its trophic action, a long-term tonic increase in tone. The mechanism largely remains to be established, but may involve altered cellular handling of hydrogen ions.