The effect of guanethidine on collagen biosynthesis in the aorta and mesenteric artery was investigated in desoxycorticosterone acetate (DOCA)-salt hypertensive rats. Prolyl hydroxylase activity (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase) and 14C-proline incorporation into collagen, two markers of collagen biosynthesis, were significantly increased in blood vessels of hypertensive rats compared with those of controls. When guanethidine (5 mg/kg, i.p.) was given daily to the hypertensive rats for 4 weeks, the blood pressure was decreased to 150 +/- 7 mm Hg, whereas the blood pressure of the untreated hypertensive rats was 218 +/- 10 mm Hg. Prolyl hydroxylase activity in the aorta and mesenteric artery and 14C-proline incorporation into aortic collagen were significantly reduced concomitant with the decrease in blood pressure. These results suggest that the decrease in vascular collagen biosynthesis in hypertensive rats treated with guanethidine is related to the lowering of their blood pressure.
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