Reduction in hypertension-induced protein synthesis in the rat pulmonary trunk after treatment with teprotide (SQ 20881).
Angiotensin II has been previously implicated as a mediator of vasoconstriction during the development of hypoxic pulmonary hypertension. The effect of angiotensin-converting enzyme inhibition with teprotide (SQ 20881) on development of pulmonary hypertension was determined by measurement of the drug's ability to modify hypertension-induced protein synthetic changes in the rat pulmonary trunk. Rats were injected with either SQ 20881 (2 mg/kg body wt every 8 hr) or saline vehicle during exposure to chronic hypoxia at 0.5 atm for either 3 or 7 days. Comparisons were made of tissue weight, absolute protein content, and in vitro synthesis of collagen and noncollagen protein of the pulmonary trunks of SQ-treated hypoxic, SQ-treated normoxic, saline-treated hypoxic, and saline-treated normoxic rats. Treatment of hypoxic rats with SQ 20881 was found to significantly decrease right ventricular pressure, tissue weight, absolute protein content, and in vitro protein synthesis after 7 days compared to saline-treated hypoxic rats. Neither right ventricular hypertrophy nor the development of polycythemia was decreased by SQ 20881 treatment.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D006346:Heart Septum / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D014176:Protein Biosynthesis; D011651:Pulmonary Artery / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013722:Teprotide / Q000494:pharmacology / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D003094:Collagen; D013722:Teprotide