Rat brain regional preproenkephalin A messenger RNA levels are altered in genetic hypertension.
Considerable neuroanatomical and pharmacological evidence suggests that preproenkephalin A-derived peptides, particularly methionine-enkephalin, are involved in regulation of the cardiovascular system in both physiological and pathological states. In this study, we used a rat preproenkephalin A complementary DNA to determine whether proenkephalin A-derived peptides participate in the pathogenesis of hypertension as reflected by brain regional messenger RNA levels. Complementary DNA clones of the rat preproenkephalin A mRNA and rat small myelin basic protein mRNA were hybridized to total RNA extracted from hypothalamus, pons-medulla, thoracic cord, midbrain, and cerebellum of 3 1/2-week-old and 12-week-old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. In 3 1/2-week and 12-week animals there were no differences in the levels of myelin basic protein messenger RNA between the two groups in any brain region. At 3 1/2 weeks, preproenkephalin A mRNA levels did not differ between normotensive and hypertensive strains. In contrast, at 12 weeks preproenkephalin A mRNA levels were increased in hypothalamus, midbrain, thoracic cord, and cerebellum of SHR relative to WKY. Preproenkephalin A mRNA was significantly reduced in the pons-medulla of SHR relative to WKY. Our findings provide evidence that alterations in brain regional preproenkephalin A mRNA levels are associated with the development of spontaneous hypertension in the rat.
Hoegler
D B
DB
Center for Cardiovascular Research, Toronto Hospital, University of Toronto, Ontario, Canada.
Sole
M J
MJ
Liew
C C
CC
D000375:Aging / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D006824:Hybridization, Genetic; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D004745:Enkephalins; D004676:Myelin Basic Protein; D011498:Protein Precursors; D012333:RNA, Messenger; C033660:preproenkephalin