Ovokinin, a peptide recently isolated from an enzymatic digest of ovalbumin, has been shown to mediate vasorelaxation of the canine mesenteric artery through bradykinin B1 receptors. Bradykinin can mediate both vasorelaxation and vasocontraction depending upon the tissue or species investigated. The aim of this study was to characterize ovokinin further by determining whether the effects of this peptide, like bradykinin, vary when using different species and tissue preparations as well as different contracting agents. Isolated aortic rings from guinea pigs, normotensive rats, and spontaneously hypertensive rats were exposed to phenylephrine, prostaglandin F2a, potassium chloride, or bradykinin. Bradykinin contracted guinea pig and spontaneously hypertensive rat aortas, however, it had no effect on normotensive rat aortas. In this study, ovokinin did not exhibit activity in any of the preparations except in guinea pigs, where it potentiated the contraction elicited by bradykinin only. This potentiation was blocked when rings were pretreated with captopril, a kininase II inhibitor. Ovokinin may also exhibit slight vasorelaxing activity in spontaneously hypertensive rat aortas precontracted with prostaglandin F2a. These findings suggest that, like bradykinin, the effects of ovokinin are species- and tissue-dependent. The action of ovokinin on the guinea pig aorta may involve kininase II, which is partly responsible for the degradation of bradykinin and other kinins. / Master of Science

Intravenous administration of ovokinin(2-7), a cleavage peptide derived from ovalbumin, dose-dependently (0.1-5 mg/kg) lowered the mean arterial pressure (MAP) that was not accompanied by a significant change in the heart rate (HR) of urethane-anesthetized rats. The hypotensive effects of ovokinin(2-7) were five orders of magnitude lower compared to that of bradykinin and were largely prevented by pretreatment with the bradykinin B2 receptor antagonist HOE140 (81.6±18.4%) and moderately affected by the B1 receptor antagonist [des-Arg10]-HOE140 (26.3±15.5%). Intracellular Ca2+ levels, as measured by Fur 2-AM, were significantly elevated in cultured aorta smooth muscle cells by ovokinin(2-7). The increases were abolished by HOE140 and unaffected by [des-Arg10]-HOE140. The elevation of intracellular Ca2+ by ovokinin(2-7) was dependent on Ca2+ entry from extracellular space as it was reduced in a Ca2+-free solution. Pretreatment of the cells with the phospholipase C inhibitor U73122 (2 μM) eliminated the Ca 2+ increase by the peptide. PA phosphohydrolase and phospholipase A2 inhibitors significantly reduced the responses as well. Our results show that ovokinin(2-7) modulates cardiovascular activity by interacting with B2 bradykinin receptors.