The turnover of total collagen in several tissues of 12-week-old normotensive and hypertensive rats was estimated by using tritium-labeled proline as a precursor. The effect of reutilization of the label was minimized by treatment with large doses of unlabeled proline subsequent to administering the radioactive imino acid. The collagen from skin, tail tendon, aorta, and mesenteric artery in normotensive animals had a half-life of about 60-70 days. In hypertensive animals the half-lives of skin and tail tendon collagen were unchanged but the half-lives of collagen in the aorta and mesenteric artery were reduced to 17 days.In previous studies from this laboratory we reported that hypertension in rats leads to an increased synthesis and deposition of collagen in arteries (1) and microvessels (2). In one set of experiments, treatment of hypertensive rats with f-aminopropionitrile, an inhibitor of collagen crosslinking, resulted in a lowering of the blood pressure within 3 weeks (3). If collagen deposition itself leads to a maintenance of the elevated pressure as we have proposed (3), then this reversal in such a short time may indicate that in hypertension collagen breakdown as well as synthesis may be accelerated. To investigate this possibility, we set about to measure the decay in specific activity of protein-bound hydroxyproline (collagen) after rats were labeled with L-[2,3-3H]proline. Many other investigators have attempted to measure collagen turnover using radioactive amino acids (4-9); however, no correction was made for reutilization of the labeled amino acid that was used. In this report we have utilized an in vivo pulse-chase experiment to minimize the problem of reutilization and have been able to estimate the turnover of collagen in several tissues of normal and hypertensive rats. Normotensive rats (12-weeks-old) with an average body weight of 373 g were kept in disposable cages in a hood. DOCA/salt hypertension was produced in uninephrectomized 6-week-ole male Wistar rats by twice weekly subcutaneous injection of DOCA (5 mg per rat) (10, 11). Rats were maintained on the standard diet and allowed free access to drinking water containing 1% NaCl. After 6 weeks of treatment their average blood pressure was 200 mm Hg (1 mm Hg = 133 Pa) and their average body weight was 416 g. During the experiments, the normotensive animals gained 120 g in 53 days and 250 g in 111 days, while the hypertensives gained 90 g in 53 days. Of the twenty rats started on the DOCA/salt regimen, five died from respiratory infections and three others could not be used because they were also infected. For this reason only three time points could be measured for the hypertensive group. Blood pressure was monitored weekly by the tail cuff microphone method with an instrument made by Hoffmann-La Roche & Co., Basel, Switzerland. MATERIALS AND METHODSBlood was obtained by either cardiac puncture or tail vein bleeding. Serum proteins were precipitated by the addition of 3 ml of 10% trichloroacetic acid per ml of serum and removed ...

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