Cardiovascular actions of dihydralazine as modified by dietary linoleic acid.
The experiments were carried out in order to examine whether the hypotensive effect of dihydralazine can be augmented by concomitant ingestion of a diet enriched with linoleic acid. After prefeeding with a linoleic acid rich diet (13.3 J%) an augmented hypotensive dihydralazine effect (11-24 mm Hg) could be observed in acute experiments in conscious (1 mg/kg i.v.) and pentobarbital-anaesthetised (4 mg/kg i.v.) normotensive rats with different duration of the feeding period as well as in conscious (1 mg/kg i.v.) spontaneously hypertensive rats relative to linoleic acid poor (0.5 J%) fed animals. This effect was abolished by pretreatment with the cyclooxygenase inhibitors indomethacin (10 mg/kg i.v.) or acetylsalicylic acid (100 mg/kg i.v.). The chronotropic dihydralazine response was with one exception not different between the two dietary groups. In chronic experiments with spontaneously hypertensive rats the augmentation of the hypotensive dihydralazine effect (1 mg/kg X d, s.c.) after linoleic acid rich diet did not attain statistical significance after a 6-weak prefeeding period. The renovasodilatory action of dihydralazine (3 mg) was increased in isolated kidney preparations of linoleic acid rich fed rats. This effect was accompanied by a shift of the prostaglandin formation toward vasodepressive PGE. We conclude that the altered cardiovascular effects of dihydralazine after linoleic acid rich diet are primarily caused by changes in the formation of prostaglandins and the activity of the sympathetic nervous system.
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004041:Dietary Fats / Q000494:pharmacology*; D004078:Dihydralazine / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006830:Hydralazine / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D013045:Species Specificity
D004041:Dietary Fats; D005227:Fatty Acids; D008041:Linoleic Acids; D010743:Phospholipids; D006830:Hydralazine; D019787:Linoleic Acid; D011464:Epoprostenol; D004078:Dihydralazine; D001241:Aspirin; D007213:Indomethacin