Tyrosine kinase inhibition suppresses angiotensin contraction in hypertensive and normotensive small resistance arteries.
Protein tyrosine kinases (PTKs) may influence vascular resistance, which is controlled primarily at the level of small arteries and arterioles. This study evaluates these kinases in resistance arteries from spontaneously hypertensive (SHR) and normotensive (WKY) rats using the protein tyrosine kinase inhibitor, tyrphostin-25. Gracilis muscle arteries (90-160 um, internal diameter) were mounted on a resistance vessel myograph and contractile responses to phenylephrine (PE) and angiotensin II (AII) were measured in the presence and absence of tyrphostin-25 (0.02-20 uM). Tyrphostin-25 inhibited AII, but not PE contractions and was less potent in the hypertensive arteries. This demonstrates for the first time that PTKs contribute to the contractile activity of resistance arteries from both hypertensive and normotensive rats. Further, results confirm in small arteries that AII-induced contractions are PTK-dependent and that arteries from hypertensive rats are hyporesponsive to PTK inhibition.
Malloy
L G
LG
Department of Biology, Bates College, Lewiston, Maine, USA.
Sauro
M D
MD
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020032:Tyrphostins; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D009570:Nitriles; D020032:Tyrphostins; D000804:Angiotensin II; C079836:tyrphostin 25; D011505:Protein-Tyrosine Kinases