A factor that initiates myocardial hypertrophy in hypertension.
A lack of correlation between blood pressure and myocardial hypertrophy was established in spontaneously hypertensive rats, suggesting that factors other than blood pressure control might be responsible for the modulation of myocardial hypertrophy. An in vitro system that is independent of blood pressure and hemodynamic effects was developed by use of isolated myocytes to study myocardial protein synthesis. The validity of this system was determined by means of morphology, by receptor integrity, and by studying the incorporation of tritiated leucine into myocyte protein (dpm/mg/hr). Addition of a supernatant of spontaneously hypertensive rat myocardial homogenate (centrifuged at 1500 g) to the myocyte system resulted in a significant increase in tritiated leucine incorporation into myocyte protein when compared with the addition of homogenates from normal controls. The protein from the homogenate was partially purified by high performance liquid chromatography. The resultant purified protein also stimulated protein synthesis by 70%. Furthermore, a significant increase in the specific activity of the transfer RNA and the rate of protein synthesis was observed after addition of homogenate from hypertrophied heart (4.02 +/- 0.3 vs 7.0 +/- 0.2 pmol leucine/microgram protein/hr; p less than 0.05). These data demonstrate the existence of a soluble factor in the hypertrophied myocardium that stimulated protein synthesis. This factor may play a key role in modulation of myocardial structure during development or regression of myocardial hypertrophy in hypertension.
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology*; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000032:analysis; D006973:Hypertension / Q000150:complications* / Q000473:pathology; D007930:Leucine / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009206:Myocardium / Q000032:analysis; D009638:Norepinephrine / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D014020:Tissue Extracts / Q000494:pharmacology*
D014020:Tissue Extracts; D000242:Cyclic AMP; D007930:Leucine; D009638:Norepinephrine