Increased Collagen Synthesis in Blood Vessels of Hypertensive Rats and Its Reversal by Antihypertensive Agents

  1. Akira Ooshima1,
  2. George C. Fuller*,
  3. George J. Cardinale1,
  4. Sydney Spector1, and
  5. Sidney Udenfriend1
  1. 1Roche Institute of Molecular Biology, Nutley, New Jersey 07110
  2. *University of Rhode Island, Department of Pharmacology, Kingston, R.I. 02881

Abstract

Collagen synthesis is increased in the aortas, mesenteric arteries, and to a lesser extent, in the hearts of rats either made hypertensive with desoxycorticosterone acetate-salt or that are spontaneously hypertensive. Several markers of collagen biosynthesis were shown to be increased, including prolyl hydroxylase (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase), prolyl hydroxylase-related antigen, total collagen content, and the incorporation of [3H]proline into total protein and into collagen. The antihypertensive agents chlorothiazide and reserpine, when administered before the onset of hypertension in the rats treated with desoxycorticosterone acetate-salt, prevented or diminished the increase in collagen biosynthesis. When reserpine was given after the onset of hypertension, prolyl hydroxylase activity was decreased concomitant with the decrease in blood pressure. Treatment with reserpine is particularly effective in diminishing arterial prolyl hydroxylase activity.

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