Sympathoadrenal control by paraventricular hypothalamic beta-endorphin in hypertension.
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.
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood*; D004058:Diffusion; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D001615:beta-Endorphin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000502:physiology
D001786:Blood Glucose; D002395:Catecholamines; D004745:Enkephalins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; D001615:beta-Endorphin