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Differences in the expression of opioid peptides in Dahl salt-resistant and salt-sensitive rats

University of British Columbia

The Dahl strain of genetically salt-resistant (R) and salt-sensitive (S) rats affords an opportunity to explore mechanisms for the development of hypertension and the consequences, as well as sensitivity or resistance, of salt-induced hypertension. Because of the evidence that opioid peptides and their receptors can be involved in cardiovascular regulation, the objective of this study was to test the hypothesis that /3-endorphin and enkephalins are involved in the development of hypertension through the determination of their precursors preproopiomelanocortin (POMC) and preproenkephalin (ppENK) messenger RNAs in this animal model. Three week old inbred Dahl R and S rats were maintained on high salt diet (8% NaCI) or low salt diet (0.4%) for six weeks. POMCmRNA and ppenk mRNA were examined from tissues of Dahl R and S rats as determinedly Northern blot analysis using p-actin as an internal standard. POMC mRNA was abundant in the pituitary tissues and was not detectable in other tissues. ppenk mRNA was abundantly present in brain, testis and heart. There was more POMC mRNA in the pituitary tissue of R rats on high salt diet compared with the pituitary of S rats on high salt diet. Differences in POMC mRNA in the pituitary were not observed between R and S on low salt diet. There were no differences of ppENK mRNA in the brain between R and S rats on high salt diet. Increased ppENK mRNA was found in the right and left ventricles of the heart of S rats on low salt diet. The increase in ppENK mRNA in the cardiac ventricles of S rats was exaggerated when they were on high salt diet. To define the role of increased ppENK mRNA in the S rats in the regulation of cardiovascular function, the effects of intravenous administration of proenkephalin-derived bioactive peptides Leu5-enkephalin (LE), Met5-enkephalin (ME), Met5-enkephalin-Arg6-Gly7-Leu5 (MEAGL), andMet5-enkephalin-Ard-Phe7 (MEAP) in Sprague-Dawley rats, and effects of these peptides on isolated intact hearts of Sprague-Dawley rats, were examined. At intravenous doses of 3.6 and 36 nmole, none of the opioid peptides had effects on arterial pressure or heart rate. Intravenous administration of LE, ME, MEAGL or MEAP at a dose of 360 nmole per animal briefly deceased the heart rate. The MEAP, but not LE, ME, or MEAGL, induced a more prolonged increase in arterial pressure at the intravenous dose of 360 nmole. LE,ME, MEAGL or MEAP, at concentration 10-6 M in the perfusion solution, had no direct effect on the developed pressure in the left ventricle of the isolated heart. These data show increased preproenkephalin mRNA in the heart and decreased POMC mRNA in the pituitary of Dahl S compared to Dahl R rats. From these results we speculate that: (1)inefficient pituitary production of POMC and consequently J3-endorphin, which is known to decrease arterial pressure, may contribute to the development of hypertension in the S rats on high salt diet; (2) increased release from the heart of the opioid peptide MEAP, and possibly other enkephalins, may be related to the high blood pressure of S rats on low salt diet; (3) exaggerated release of MEAP and/or other enkephalins may exacerbate the process of hypertension in S rats on high salt diet.

Thesis/Dissertation

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2008-09-10

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http://hdl.handle.net/2429/1763

Medicine

University of British Columbia

UBCV

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