Methionine enkephalinergic neuronal activity in cerebral nuclei of spontaneously hypertensive rats.

Abstract

SUMMARY The role of methionine enkephalin (ME) neurons in the development of genetic hypertension in SHR is the subject of this study. Methionine enkephalin-like immunoreactivity (MELI) and ME receptor binding (MERB) levels were assayed quantitatively by microdensitometry of fluorescence micrographs and autoradiographs of 85 cerebral nuclei and areas of both young and adult spontaneously hypertensive rats (SHR). Normotensive Wistar Kyoto rats (WKY) were used as controls. In young SHR, both MELI and MERB levels were markedly higher in the n. dorsal is nervi vagi, n. amygdaloideus medial is, and group of stria terminal nuclei than in those of young WKY, while both levels were lower in the n. reticularis lateralis, n. corporis mamillaris lateralis, and n. arcualus. MELI levels in the tractus spinalis nervi trigemini and MERB in the n. tractus spinalis nervi trigemini and median eminence were also lower in young SHR, whereas MERB in the n. amygdaloideus central is was higher. Alteration in these nuclei was no longer detectable in adult SHR. Whereas in adult SHR, both MELI and MERB levels in the n. reticularis medialis were higher than those of adult WKY, and MELI in the n. accumbens septi and MERB in the n. caudatus were also higher, while MELI in the area lateral is hypothalami was lower than that in adult WKY. The findings indicate that activation of ME neurons in the n. dorsal is nervi vagi and limbic area and also a decrease in ME neuronal activity in the area spinalis nervi trigemini, n. reticularis lateralis, and n. arcuatus may be causally related to the development of hypertension and hyperreactivity in SHR. (Hypertension 4: 662-669, 1982) KEY WORDS • methionine enkephalin • blood pressure • hypertension • SHR I NCREASING evidence is being accumulated that endogenous opiate neurons in the brain may be involved in cardiovascular regulation. Administration of stable methionine enkephalin (ME) analogs and B-endorphin into the cisterna magna produces an initial and transient increase in blood pressure and heart rate followed by a delayed hypotension and bradycardia in anesthetized dogs' and causes preferential hypotensive effects in anesthetized rats.2 ME and leucine enkephalin (LE) produces preferential vasopressor effects in anesthetized rats 2 and conscious rats. In spontaneously hypertensive rats (SHR), the pressor response to LE 4 or |D-Ala]-ME 9 is markedly greater than in normotensive Wistar Kyoto rats (WKY). Only in SHR but not in WKY, administration of either naloxone or naltrexone inhibits the hypotension produced by clonidine or a-methyldopa. 10 Clondine and a-methylnorepinephrine increase the release of B-endorphin immunoreactivity from slices of the brainstem of SHR but not that of WKY." All these findings suggest that the endogenous opiate neurons are somehow altered in the brain of SHR.The present study was designed to clarify ME neuronal alteration by measuring methionine enkephalinlike immunoreactivity (MELI) and methionine enkephalin receptor binding (MERB) in various cerebral nuclei of both...