Feuerstein G, Zerbe R L, Faden A I
Hypertension. 1983 Sep-Oct;5(5):663-71. doi: 10.1161/01.hyp.5.5.663.
This study examined the cardiovascular, respiratory, and sympathetic effects of selective mu and delta opioid agonists microinjected into the hypothalamic nucleus preopticus medialis (POM) of conscious SHR and WKY rats. The mu receptor agonist D-Ala2-MePhe4-Gly5-ol-enkephalin (DAGO) at a dose of 0.6 or 6.0 nanomoles (Nmol) increased the blood pressure and heart rate in WKY rats. In SHR rats, the lower dose of DAGO similarly had a pressor effect whereas the higher dose was depressor; heart rat was increased only by the 6.0 nmol dose in these animals. In both SHR and WKY rats, this opioid caused respiratory acidosis and elevation of plasma norepinephrine (NE) and epinephrine (E); plasma vasopressin was reduced by the higher dose of DAGO. All of these effects of the mu agonist were reversed by the opiate receptor antagonist naloxone (0.5 mg/kg, i.a.). The delta opiate-receptor agonist D-Ala2-D-leu5-eukephalin at a dose of 6.0 or 20.0 nmol increased blood pressure and heart rate in both SHR and WKY rats without affecting respiratory variables. Plasma NE and EPI were elevated at the peak of the pressor period. These studies suggest that the anteroventral hypothalamic region may be an important site in central autonomic regulation by opioid peptides. The mu-receptor agonist was more potent than the delta agonist in eliciting cardiovascular and respiratory effects and associated sympatho-adrenomedullary activation.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究检测了选择性μ和δ阿片受体激动剂微量注射到清醒的自发性高血压大鼠(SHR)和Wistar-Kyoto大鼠(WKY)的下丘脑视前内侧核(POM)后对心血管、呼吸及交感神经的影响。μ受体激动剂D-丙氨酸2-甲基苯丙氨酸4-甘氨酸5-亮氨酸脑啡肽(DAGO),剂量为0.6或6.0纳摩尔(Nmol)时可使WKY大鼠血压和心率升高。在SHR大鼠中,较低剂量的DAGO同样有升压作用,而较高剂量则有降压作用;这些动物中只有6.0 nmol剂量可使心率升高。在SHR和WKY大鼠中,该阿片类药物均可引起呼吸性酸中毒以及血浆去甲肾上腺素(NE)和肾上腺素(E)升高;较高剂量的DAGO可使血浆血管升压素降低。μ激动剂的所有这些作用均可被阿片受体拮抗剂纳洛酮(0.5 mg/kg,腹腔注射)逆转。δ阿片受体激动剂D-丙氨酸2-D-亮氨酸5-脑啡肽,剂量为6.0或20.0 nmol时可使SHR和WKY大鼠的血压和心率升高,且不影响呼吸变量。在升压期峰值时血浆NE和EPI升高。这些研究提示,下丘脑腹前区可能是阿片肽进行中枢自主调节的重要部位。在引发心血管和呼吸效应及相关交感-肾上腺髓质激活方面,μ受体激动剂比δ激动剂更有效。(摘要截短于250字)