EFFECT OF MODULATORS OF PROTEIN-TYROSINE KINASE-ACTIVITY ON GENDER-RELATED DIFFERENCES IN VASCULAR REACTIVITY AT REDUCED TEMPERATURE

We used the isolated-muscle-bath technique to examine the effect of pr otein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) inh ibitors on the response of rings of tail artery from male and female r ats to cooling and reduced temperature in the absence and presence of two PTK-dependent (clonidine and serotonin) and one PTK-independent (p henylephrine, PE) agonists. At 37 degrees C, reactivity to clonidine, serotonin, and PE was the same in tail artery from female and male rat s. At 25 degrees C, reactivity to clonidine and serotonin, but mt PE, was greater in tail artery from Female rats compared with those from m ale rats. Sodium orthavanadate (SOV) eliminated the gender-related dif ference in the contractile effect of clonidine and serotonin at 25 deg rees C. The sensitivity to relaxation by genistein was considerably gr eater for clonidine and serotonin at both temperatures as compared wit h PE. At 25 degrees C the sensitivity to genistein was greater for the clonidine and serotonin-contracted rings from female rats. In the pre sence of SOV, temperature reduction led to contraction of rat-tail art ery. This effect was greater in rings from female rats. Our results st rongly implicate differences in the activity of the PTK transduction p athway as the cause of the observed gender-related differences in agon ist-mediated contraction at 25 degrees C and in cold-induced vasoconst riction.