Tyrosine kinases contribute to vascular smooth muscle contraction by increasing calcium sensitivity and increasing calcium entry. Previous work suggests ₂-adrenoreceptors (₂-AR) contract arteries in part by activating one or more tyrosine kinases. We have demonstrated enhanced contractile sensitivity to the ₂-AR agonist, UK14304 in arteries from rats made hypertensive with chronic nitric oxide synthase inhibition (LHR) compared to arteries from normotensive Sprague-Dawley rats (NR) and that this contraction relies on calcium entry. We hypothesized that one or more tyrosine kinases augment ₂-AR contraction in LHR arteries by increasing calcium and not by enhancing calcium sensitivity. The tyrosine kinase inhibitor tyrphostin 23 significantly and concentration-dependently attenuated UK14304 contraction of both NR and LHR denuded thoracic aorta rings. However, tyrphostin 23 did not alter UK14304 augmentation of contraction in ionomycin-permeabilized aorta, indicating that tyrosine kinases regulate intracellular calcium concentration, not calcium sensitivity. The src family inhibitor PP1 and the EGF receptor kinase inhibitor, AG1478 did not alter ₂-AR contraction, while MEK inhibitor PD98059 attenuated the contraction. Contraction to CaCl₂ in ionomycin permeabilized LHR rings was greater than in NR rings. UK14304 augmented CaCl₂ contraction in ionomycin permeabilized rings from both groups, but to a greater extent in LHR aorta. Together, these data suggest that ₂-AR stimulate contraction through two separate pathways. One, apparently enhanced with NOS inhibition hypertension, mediates activation of calcium sensitivity and is independent of tyrosine kinase activation. The other is tyrosine kinase dependent and regulates intracellular calcium concentration.