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.
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
P M
PM
Schiffers
H A
HA
van der Heijden
G E
GE
Fazzi
H A
HA
Boudier
J G
JG
De Mey
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D007537:Isometric Contraction / Q000187:drug effects; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000294:innervation; D051381:Rats; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000187:drug effects* / Q000294:innervation; D013564:Sympathetic Nervous System / Q000502:physiology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D014662:Vasoconstrictor Agents; D000804:Angiotensin II