Cardiovascular responses to intrathecal administration of endomorphins in anesthetized rats.
Endomorphins (EMs), the endogenous, potent and selective mu-opioid receptor agonists, have been shown to decrease systemic arterial pressure (SAP) in rats after intravenous (i.v.) administration. In the present study, cardiovascular responses to intrathecal (i.t.) injection of EMs were investigated in urethane-anesthetized rats. It is noteworthy that EMs elicited decreases in SAP and heart rate (HR) in a dose-dependent manner; 10-300nmol/kg were injected intrathecally. Furthermore, these vasodepressor and bradycardic effects were significantly antagonized by naloxone (0.5mg/kg, i.t.). Interestingly, i.t. (5mg/kg) or i.v. (50mg/kg) administrations of N(omega)-nitro-l-arginine methylester (l-NAME) attenuated the vasodepressor and bradycardic effects. Moreover, pretreatment of the rats with muscarinic receptor antagonist atropine (2mg/kg, i.v.) and alpha-adrenoceptor antagonist phentolamine (1mg/kg, i.v.) significantly reduced the vasodepressor effects of EMs. Nevertheless, pretreatment with beta-adrenoceptor antagonist propranolol (2mg/kg, i.v.) could only block the bradycardia effects induced by EMs, but had no significant effects on the hypotension. In summary, all the results suggested that i.t. administration of EMs decreased SAP and HR which were possibly mediated by the activation of opioid receptors in the rat spinal cord. In addition, nitric oxide (NO) release in both the spinal cord and in peripheral tissues might regulate the cardiovascular activities of EMs, and the muscarinic receptor and adrenoceptor played an important role in the regulation of the cardiovascular responses to i.t. administration of EMs.
Wang
Chang-Lin
CL
Key Laboratory of Preclinical Study for New Drugs of Gansu Provinces, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, China.
Yu
Ye
Y
Lai
Lu-Hao
LH
Cui
Yun
Y
Wang
Xiang
X
Wang
Rui
R
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007278:Injections, Spinal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D010646:Phentolamine / Q000008:administration & dosage / Q000494:pharmacology; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000701:Analgesics, Opioid; D009842:Oligopeptides; C105293:endomorphin 1; D009270:Naloxone; D001285:Atropine; D011433:Propranolol; D019331:NG-Nitroarginine Methyl Ester; D010646:Phentolamine