POMC biosynthesis in the intermediate lobe of the spontaneously hypertensive rat.
Pro-opiomelanocortin (POMC) synthesized in the anterior (AL) and intermediate lobe (IL) of the rat pituitary gland, is a prohormone precursor of several peptide hormones that may participate in the regulation of blood pressure. We therefore studied the biosynthesis of POMC by measuring the incorporation of 3H-tyrosine into the IL of 32-week-old spontaneously hypertensive rat (SHR) of the Aoki-Okamoto strain and their normotensive controls, the Wistar-Kyoto rat (WKY). Under basal conditions, POMC biosynthesis was significantly reduced in the SHR (1130 +/- 102 cpm/30 min/IL, n = 13) when compared to the WKY (1515 +/- 163 cpm/30 min/IL, N = 12, P less than 0.05, t test). There was also an inverse correlation between systolic blood pressure and POMC biosynthesis in both the WKY (Y = 8.4 +/- 1.38X + 2097 +/- 673, r = 0.86 +/- 0.06, N = 5), and SHR (Y = 5.7 +/- 1.8X + 1122 +/- 336 r = 0.57 +/- 0.13, N = 3). The decreased POMC biosynthesis was associated with a higher dopamine content in IL in SHR compared to WKY (1.56 +/- 0.53, n = 17 v 0.51 +/- 0.16, n = 17 pmol/IL, P less than 0.05, Mann-Whitney test). Oral administration of three different antihypertensive agents (propranolol, captopril, or hydralazine) for 12 weeks normalized blood pressure and POMC biosynthesis in the SHR but had no effect on either variable in the WKY. Because POMC biosynthesis in IL increased with normalization of blood pressure in the SHR, the decreased POMC biosynthesis in SHR may be a consequence rather than a cause of the elevated blood pressure in SHR.
Felder
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RA
Department of Pathology, University of Virginia Medical Center, Charlottesville 22908.
Garland
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DS
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001923:Brain Chemistry; D002216:Captopril / Q000494:pharmacology; D004298:Dopamine / Q000032:analysis; D006830:Hydralazine / Q000494:pharmacology; D008297:Male; D010902:Pituitary Gland / Q000032:analysis / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000032:analysis / Q000096:biosynthesis*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000521:alpha-MSH / Q000032:analysis
D000959:Antihypertensive Agents; D006830:Hydralazine; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D002216:Captopril; D011433:Propranolol; D004298:Dopamine