| Endomorphins, the endogenous, potent 和 selective n-opioid receptor agonists, have been shown to decrease systemic arterial pressure (SAP) in rats. In the present study, responses to endomorphins were investigated in systemic vascular bed of alloxan-induced diabetic rats and in non-diabetic rats. Diabetes was induced by alloxan (220mg/kg, i.p.) in male Wistar rats. At 4~5 weeks after the onset of diabetes, intravenous injections of endomorphins (1~30nmol/kg) led to an increase of SAP and heart rate (HR) consistently and dosed-dependently. Similar changes were observed in response to endomorphin2. The hypertension could be antagonized markedly by i.p. 2mg/kg of naloxone. On the other hand, bilateral vagotomy would attenuate the effects of hypertension and diminished the changes of HR in response to endomorphins. With diabetic rats, 6~10 weeks after the induction of diabetes, intravenous injections of endomorphins produced non-dose-related various changes in SAP, such as a single decrease, or a single increase, or biphasic changes characterized by an initial decrease followed by a secondary increase, or no change at all. These results suggest that diabetes may lead to the dysfunction of the cardiovascular system in response to endomorphins. Furthermore, the diabetic rats of 4~5 weeks after alloxan-treatment, the increase in SAP and HR caused by i.v. endomorphins might be explained by a changed effect of vagus and by a naloxone-sensitive mechanism.We compared the inhibitory effects of endomorphins (EMs) on the electrical field stimulation (EFS)-induced cholinergic bronchoconstriction in normal rats and diabetic rats. EFS elicited a frequency-dependent contractile response in normal and alloxan-induced diabetic rats. These EFS-induced bronchoconstrictions were completely abolished by tetrodotoxin (1μM) or atropine (1μM), which indicates that these contractile responses are cholinergic components At 4-weeks after the onset of diabetes, the EFS- induced bronchoconstriction in diabetes in vitro were greater that that in non-diabetes rats. EMs inhibited the response to EFS in rat isolated bronchus in a concentration- and frequency-dependent manner in normal rats and diabetic rats, however, The percentage inhibition induced by EM2 was slightly lower comparedwith that of EMI. It is therefore considered that the inhibition effects of EMI and EM2 may take place at frequencies under physiological conditions. Furthermore, both in diabetic and non-diabetic rats, EMI and EM2 (0.01-10|aM) induced inhibition of cholinergic constriction in a dose-dependent manner at 1, 2 and 4 Hz. The inhibitory effect on EFS was blocked by the opioid receptor antagonist naloxone (IO^iM), indicating that opioid receptors were involved. However, the inhibitory effects of EMs on the EFS-induced bronchoconstriction in diabetes were significantly weaker than those in non-diabetes. Both EMI and EM2 (l^M) had no effect on the contractile response to exogenous ACh, indicating a prejunctional effect. 8 weeks after the induction of diabetes, both the EFS- and exogenous ACh-induced bronchoconstrictions in diabetes were further enhanced compared to those in short-time (4 weeks) diabetic rats. Moreover, the inhibitory effects of EMI and EM2 on the EFS-induced bronchoconstriction were further attenuated. These results suggest that dysfunction of presynaptic inhibitory modulation through opioid receptor by EMs may take place in the bronchus of diabetic rtas.
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