In vivo effects of angiotensin II on vascular smooth muscle contraction and blood pressure are mediated through a protein tyrosine-kinase-dependent mechanism.
The effects of in vivo angiotensin II (AII) treatment on protein tyrosine kinase (PTK) levels were examined. It was found that administration of AII to normotensive Wistar-Kyoto rats induced tyrosine phosphorylation in aorta in a time-dependent manner. There was a rapid increase in phosphotyrosine content as early as 1 min, with peak phosphorylation occurring between 5 and 10 min. The response was also dose dependent, with increases in phosphorylation levels from 1 to 1000 micrograms/kg AII. Tyrosine phosphorylation was blocked using the angiotensin type 1 receptor antagonist losartan (10 mg/kg), suggesting that the effects are receptor mediated. Tyrphostin-25 (100 microM), a selective inhibitor of PTKs, when given in vivo was also able to attenuate phosphorylation by AII, further suggesting a PTK-mediated event. To couple these biochemical changes with physiological events, we also examined the ability of AII to induce vasoconstriction and raise systolic blood pressure through a PTK-mediated mechanism. In addition to increasing phosphorylation levels, AII caused a rise in systolic pressure in vivo and induced contraction in vitro. Both of these responses could be attenuated by pretreatment with losartan or tyrphostin-25. This is the first demonstration of the effects of AII on tyrosine phosphorylation in vivo. The data suggest that AII may induce a pressor response at least in part through activation of PTKs and subsequent phosphorylation of smooth muscle contractile proteins or activation of other protein kinases.
Sauro
M D
MD
Department of Anesthesiology, State University of New York Health Science Center, Syracuse, USA.
Sudakow
R
R
Burns
S
S
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D051381:Rats
D000804:Angiotensin II; D011505:Protein-Tyrosine Kinases