Jin C B, Rockhold R W
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Hypertension. 1991 Oct;18(4):503-15. doi: 10.1161/01.hyp.18.4.503.
The paraventricular hypothalamus regulates autonomic nerve outflow and is innervated with beta-endorphin-immunoreactive nerve terminals. This study examined the effects of beta-endorphin microinjected into the paraventricular hypothalamus on blood pressure, heart rate, and plasma catecholamine and glucose concentrations in conscious, unrestrained spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at the age of about 9 weeks. Thirty minutes after paraventricular hypothalamic injection of [125I] beta-endorphin (3.5 micrograms), most of the recovered radioactivity was detectable within +/- 0.5 mm from the injection site in the coronal, sagittal, and horizontal planes. Unilateral paraventricular hypothalamic injections of beta-endorphin (1 and 0.1 microgram/0.1 microliter) increased blood pressure and heart rate in both strains in a dose-independent manner with significantly greater increases in SHR. Plasma catecholamine and glucose concentrations were measured 15, 30, and 60 minutes after beta-endorphin injection. Norepinephrine concentrations were not significantly altered in WKY rats but increased in SHR. Epinephrine concentrations increased in both strains with significantly greater increases in SHR. Increases in catecholamine concentrations were not dose-related. Glucose concentrations also increased in both strains with significantly greater increases in SHR only at the lower dose. Ganglionic blockade with pentolinium significantly reduced beta-endorphin-induced pressor and tachycardiac responses in SHR. Pretreatment of the paraventricular hypothalamus with naltrexone (1.1 micrograms) in SHR blocked the initial pressor and tachycardiac responses to beta-endorphin (0.1 microgram) and blunted increases in epinephrine and glucose levels. When the animals were anesthetized with alpha-chloralose 2-5 days after the study in conscious animals, there were no differences in blood pressure or heart rate between strains after beta-endorphin (0.1 microgram) injection. The results indicate that conscious SHR show enhanced cardiovascular and sympathoadrenal responses to beta-endorphin injected into the paraventricular hypothalamus, suggesting that alterations in the activity of the paraventricular hypothalamic beta-endorphin system can modulate the development of hypertension in SHR.
室旁下丘脑调节自主神经输出，并接受β-内啡肽免疫反应性神经末梢的支配。本研究检测了向约9周龄清醒、不受束缚的自发性高血压大鼠（SHR）和Wistar-Kyoto（WKY）大鼠的室旁下丘脑微量注射β-内啡肽对血压、心率、血浆儿茶酚胺和葡萄糖浓度的影响。在室旁下丘脑注射[125I]β-内啡肽（3.5微克）30分钟后，在冠状面、矢状面和水平面距注射部位±0.5毫米范围内可检测到大部分回收的放射性。单侧室旁下丘脑注射β-内啡肽（1和0.1微克/0.1微升）以剂量非依赖性方式增加了两种品系的血压和心率，SHR的升高幅度明显更大。在注射β-内啡肽后15、30和60分钟测量血浆儿茶酚胺和葡萄糖浓度。WKY大鼠的去甲肾上腺素浓度无显著变化，但SHR升高。两种品系的肾上腺素浓度均升高，SHR的升高幅度明显更大。儿茶酚胺浓度的升高与剂量无关。两种品系的葡萄糖浓度也升高，仅在较低剂量时SHR的升高幅度明显更大。用潘托铵进行神经节阻断显著降低了SHR中β-内啡肽诱导的升压和心动过速反应。在SHR中用纳曲酮（1.1微克）预处理室旁下丘脑可阻断对β-内啡肽（0.1微克）的初始升压和心动过速反应，并减弱肾上腺素和葡萄糖水平的升高。在清醒动物研究后2 - 5天用α-氯醛糖麻醉动物时，注射β-内啡肽（0.1微克）后品系间的血压或心率无差异。结果表明，清醒的SHR对注入室旁下丘脑的β-内啡肽表现出增强的心血管和交感肾上腺反应，提示室旁下丘脑β-内啡肽系统活性的改变可调节SHR高血压的发展。
