TYROSINE KINASE INHIBITION SUPPRESSES ANGIOTENSIN CONTRACTION IN HYPERTENSIVE AND NORMOTENSIVE SMALL RESISTANCE ARTERIES

Protein tyrosine kinases (PTKs) may influence vascular resistance, whi ch is controlled primarily at the level of small arteries and arteriol es. This study evaluates these kinases in resistance arteries from spo ntaneously hypertensive (SHR) and normotensive (WKY) rats using the pr otein tyrosine kinase inhibitor, tyrphostin-25. Gracilis muscle arteri es (90-160 um, internal diameter) were mounted on a resistance vessel myograph and contractile responses to phenylephrine (PE) and angiotens in II (AII) were measured in the presence and absence of tyrphostin-25 (0.02-20 uM). Tyrphostin-25 inhibited AII, but not PE contractions an d was less potent in the hypertensive arteries. This demonstrates for the first time that PTKs contribute to the contractile activity of res istance 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 hyporespons ive to PTK inhibition.