The Cardiovascular Effects Of Dual Peptidase Inhibitor Opiorphin In Rats

Human opiorphin is a natural peptidase inhibitor and its physiological functions have not been well characterized, it was identified in human saliva by Wisner. It's a QRFSR peptide that inhibits both human neutral ecto-endopeptidase(hNEP, EC 3.4.24.11) and human ecto-aminopeptidase(human ecto-aminopeptidase, hAP-N, EC 3.4.11.2). In present study, we attempted to investigate the effects and underlying mechanisms of human opiorphin on cardiovascular activity at peripheral level in anesthetized rats. Intravenous injections (i.v.) of opiorphin (50,100,150,200,300 nmol/kg) dose-dependently induce increases of both mean arterial pressure (MAP) and heart rate (HR). Angiotensin converting enzyme inhibitor captopril (10mg/kg, i.v.) and angiotensinâ…¡(Angâ…¡) receptor antagonist valsartan (10mg/kg, i.v.) largely abolished the hypertensive and tachycardic reponses caused by opiorphin (200, 300nmol/kg). In addition, the hypertensive effect to opiorphin was respectively partly blocked by pretreatment with phentolamine (2 mg/kg, i.v.), reserpine (0.5mg/kg, i.p.) and propranolol (2mg/kg, i.v.). However, reserpine and propranolol significantly inhibited the tachycardic response caused by opiorphin, but phentolamine didn't. Nevertheless, pretreatment with opioid receptor antagonist naloxone (2mg/kg, i.v.) did not significantly alter the cardiovascular effects of opiorphin. The results suggested that the hypertensive and tachycardic responses to opiorphin would be mainly mediated by circulatory angiotensin system and sympathetic nervous system. Opiorphin could be a good material employed to investigate the mechanism of cardiovascular responses.