Decreased sensitivity of aorta from hypertensive rats to vasorelaxation by tyrphostin.
The role of protein tyrosine kinases (PTKs) in vascular smooth muscle (VSM) contraction was examined in spontaneously hypertensive rats (SHRs). Aorta from SHRs was hyperresponsive to PTK-mediated contraction relative to normotensive Wistar-Kyoto rats (WKYs). Aorta from SHR was also hyporesponsive to vasorelaxation by tyrphostin, a selective inhibitor of PTKs. Further, we found alterations in PTK activity in aorta from SHRs. PDGF stimulated PTK activity to a greater extent in the SHR. Tyrphostin inhibited PDGF-induced PTK stimulation in both strains, however, activity returned to basal levels in the WKY only. The results suggest that PTKs may be involved in VSM contraction and in the development of hypertension.
Sauro
M D
MD
Department of Immunology and Molecular Biology, Masonic Medical Research Laboratory, Utica, NY 13501.
Thomas
B
B
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D002396:Catechols / Q000494:pharmacology*; D004347:Drug Interactions; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012680:Sensitivity and Specificity; D020032:Tyrphostins
D002396:Catechols; D009570:Nitriles; D010982:Platelet-Derived Growth Factor; D020032:Tyrphostins; C060152:tyrphostin 47; D011505:Protein-Tyrosine Kinases