Search

The present study was performed to investigate the peripheral cardiovascular effects of opiorphin in anesthetized rats. Intravenous (i.v.) injection of opiorphin (50−500 nmol/kg) caused marked dose-dependent increase in blood pressure and heart rate. The pressor and tachycardic responses induced by opiorphin (300 nmol/kg, i.v.) were significantly decreased by pretreatment with angiotensin-converting enzyme inhibitor captopril or angiotensin II type 1 (AT1) receptor antagonist valsartan, which suggested that endogenous angiotensin may be involved in the response to opiorphin. Pretreatment with α-adrenoreceptor antagonist phentolamine and β-adrenoceptor antagonist propranolol respectively attenuated the pressor response induced by opiorphin. Propranolol, but not phentolamine, inhibited the tachycardic response. Moreover, reserpine blocked both responses to opiorphin. These findings indicated that the effects of opiorphin to increase blood pressure and heart rate might be due to the stimulation of sympathetic ganglia. Additionally, studies with bilaterally adrenalectomized rats showed that adrenal medulla may be involved in the cardiovascular regulation of opiorphin. In addition, pretreatment with nonselective opioid receptor antagonist naloxone did not modify the cardiovascular responses to opiorphin, suggesting that the effects of opiorphin were not related to the opioid system. Furthermore, radioimmunoassay (RIA) showed that opiorphin significantly increased endogenous levels of angiotensin II and angiotensin III. In summary, all the results indicate that the cardiovascular effects induced by opiorphin are mediated through the renin–angiotensin system (RAS), the sympathetic ganglia and adrenal medulla, but not the opioid system. [ABSTRACT FROM AUTHOR]