Tyrosine kinase inhibitors modulate agonist-induced vasodilation in the hamster cheek pouch.
The purpose of this study was to determine whether inhibitors of tyrosine kinase attenuate vasodilation elicited by endogenously elaborated and exogenously applied nitric oxide in the in situ peripheral microcirculation. Using intravital microscopy, we found that pretreatment with genistein (1.0 microM) and tyrphostin 25 (10.0 microM), two structurally unrelated tyrosine kinase inhibitors, significantly attenuated acetylcholine-, bradykinin- and nitroglycerin-induced dilation of second-order arterioles (51 +/- 1 microm) in the in situ hamster cheek pouch (P < 0.05). Both inhibitors nearly abrogated acetylcholine-induced responses but only partially blocked bradykinin- and nitroglycerin-induced vasodilation. Genistein and tyrphostin 25 alone had no significant effects on resting arteriolar diameter and on adenosine-induced vasodilation in the cheek pouch. On balance, these data indicate that tyrosine kinase inhibitors attenuate endogenously elaborated and exogenously applied nitric oxide-induced vasodilation in the in situ hamster cheek pouch. However, the extent of tyrosine kinase inhibitor-sensitive pathway involvement in this response appears to be agonist dependent.
Ikezaki
H
H
Department of Medicine, University of Illinois at Chicago, and West Side Department of Veterans Affairs Medical Center, Chicago, Illinois 60612, USA.
Akhter
S R
SR
Hong
D
D
Suzuki
H
H
Gao
X P
XP
Rubinstein
I
I
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D020032:Tyrphostins / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D020032:Tyrphostins; D009569:Nitric Oxide; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D005996:Nitroglycerin; D000241:Adenosine; D000109:Acetylcholine