Increased preproenkephalin mrna in the heart in cardiac hypertrophy
in the dahl rat and the effects on blood pressure of the peptide
products of ppenk.
Hao, Jing Ming, and Simon W. Rabkin.
University of British Columbia, Department of Medicine, Division of
Cardiology, Vancouver, B.C., Canada
APStracts 3:0397H, 1996.
The objective of this study was to examine the expression of
preproenkepkalin (ppENK) in the heart in cardiac hypertrophy and the
effects on cardiac contractility and blood pressure regulation of its
peptide products. The ppENK-derived peptides Leu5-enkephalin (LE),
Met5-enkephalin (ME), Met5-enkephalin-Arg6-Gly7-Leu8 (MEAGL) and
Met5-enkephalin-Arg6-Phe7 (MEAP) were administered i.v.to
unanesthetized Sprague Dawley rats and to the isolated heart
preparation in the same species. LE, ME, MEAGL or MEAP, 360 nmoles
i.v., produced an immediate decrease in heart rate reaching its
maximum within 10 sec and returning to baseline by 30 sec. The blood
pressure response for each enkephalins was a small initial decrease
followed by a marked and significant (p<0.05) increase that
was for MEAP. In the isolated heart preparation, neither LE, ME,
MEAGL or MEAP altered left ventricular contractility. Cardiac
hypertrophy was produced in the Dahl salt dependent model of
hypertension with significantly (p<0.05) greater heart
weight/body weight in the Dahl S compared to Dahl R rat on a high
salt diet. Tissue RNA was extracted and Northern blot analysis
identified and quantitated mRNA using a 0.93 kb cDNA of ppENK A.
There was more ppENK mRNA in the left than right ventricle and much
less in the atria than the ventricles. The amount of ppENK mRNA was
markedly and significantly (p<0.05) increased in the left
ventricle of the Dahl S compared to Dahl R rat. In contrast, there
were no differences in ppENK mRNA levels in different brain regions
between R and S rats on high NaCl diet. Interestingly, a larger ppENK
mRNA of 1.75 kb was abundantly expressed in testicular tissue. These
data showing increased ppENK expression raise the possibilities of
(i) an autocrine/paracrine role for enkephalins in cardiac
hypertrophy (ii) an endocrine role, for the hypertrophic heart, with
increased production of enkephalins, especially MEAP, which produces
vasoconstriction and further increases in blood pressure.
Received 21 February 1995; accepted in final form 1 September
1996.
APS Manuscript Number H161-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996