Non-cardiac nucleic acid composition and protein synthesis rates in hypertension: studies on the spontaneously hypertensive rat (SHR) model

Various studies have shown the involvement of extracardiac tissues in hyper tension, including the hepato-intestinal tract, musculo-skeletal system, sk in, and the kidney. It was our hypothesis that these perturbations in non-c ardiac tissues would also include alterations in protein metabolism. Thus, the reported differences in soleus contractile protein composition may he r elated to changes in muscle protein synthesis or reduced protein synthetic efficiencies. The aim of the present study was to characterise tissue compo sition of nucleic acids and rates of protein synthesis in non-cardiac tissu es, such as liver, skeletal muscle (i.e., the Type I fibre-predominant sole us and Type II fibre-predominant plantaris), kidney, bone (tibia), skin and the gastrointestinal tract in a genetic model of hypertension (i.e., spont aneously hypertensive rats (SHRs), 15 weeks old) compared to their genetic aged-matched counterparts, i.e., normotensive Wistar-Kyoto (WKY) controls. Rates of protein synthesis were measured in vivo after injection with a flo oding dose of L-[4-H-3]phenylalanine. The results showed changed tissue wet weights (g per organ) for plantaris ( + 10%, P < 0.05), liver ( + 25%, P < 0.01), brain (-9%, P < 0.01), jejunum ( + 39%, P < 0.001) and tibia ( + 17 %, P < 0.001) in SHRs compared to WKY controls. Protein content (g or mg pe r organ) was increased in the liver ( + 32%, P < 0.01) and tibia ( + 37%, P < 0.05). RNA contents (mg per organ) were increased in plantaris ( + 17%, P < 0.01), liver ( + 22%, P < 0.01) and jejunum (+ 11%, P < 0.05). DNA (mg per organ) was increased in plantaris (+ 16%, P < 0.025) and jejunum (+ 12% , P < 0.025). The protein synthetic capacities (i.e., C-s, mg RNA/g protein ) were higher in soleus ( + 41%, P < 0.01) and plantaris (+ 6%, P < 0.05) m uscles of SHRs compared to WKYs, whereas values were lower in liver (- 11%, P < 0.01) and kidney (-6%, P < 0.01) of SHRs compared to WKYs. The fractio nal rate of protein synthesis (i.e., k(s), the percentage of the protein po ol renewed each day) was not significantly different for any of the tissues , though the rate of protein synthesis per unit RNA (i.e., k(RNA), mg prote in/day per mg RNA) was reduced in the soleus (-24%, P < 0.05) and the synth esis rate per unit DNA, i.e., k(DNA) (mg protein/day per mg DNA) was increa sed in the tibia ( + 31%, P < 0.025). This is the first report of significa nt differences between indices of protein metabolism in extracardiac tissue s in hypertension, which may reflect endocrine factors and/or the systemic influence of hypertension per se. (C) 2000 Elsevier Science B.V. All rights reserved.