ABSTRACT
OBJECTIVE: To determine whether 6 weeks continuous treatment with an angiotensin converting enzyme (ACE) inhibitor reduced renal vascular responsiveness in vivo, since this treatment results in extensive phenotypic conversion of afferent arteriolar cells from contractile to endocrine-like, renin secretory cells. METHODS: Enalapril (10 microg/kg per h s.c.) was delivered continuously for 6 weeks. In anaesthetized rabbits (treated or sham), arterial blood pressure and renal blood flow were measured and renal responsiveness tested by constructing dose-response curves to bolus doses of phenylephrine, angiotensin II and acetylcholine delivered directly into the renal artery. RESULTS: ACE inhibition resulted in a significant shift to the left in the renal vascular conductance responses to acetylcholine (P < 0.005) and angiotensin II (P < 0.05), indicating enhanced, not reduced, responsiveness to these agents. There were no significant effects of chronic ACE inhibition on the conductance responses to phenylephrine. CONCLUSIONS: Contrary to our hypothesis, 6 weeks ACE inhibition did not reduce renal vascular responsiveness to three vasoactive agents, suggesting that the phenotypic changes observed in the afferent arterioles and to a lesser extent the interlobular arteries, were either insignificant or compensated for by other changes in renal circulatory control.
Subject(s)
Acetylcholine/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Enalapril/pharmacology , Renal Circulation/drug effects , Vasodilator Agents/pharmacology , Angiotensin II/pharmacology , Animals , Arterioles/drug effects , Arterioles/pathology , Kidney/drug effects , Kidney/pathology , Rabbits , Renal Artery/drug effects , Renal Artery/pathology , Time Factors , Vascular Resistance/drug effects , Vasoconstrictor Agents/pharmacologyABSTRACT
Equivalent doses of dexamethasone, prednisolone, and betamethasone were given intraperitoneally to pregnant rats on day 20. Six dosage levels were selected: 0.4, 0.8, 1.6, 3.2, 6.4, and 12.8 mg/kg. Corticosteroids were diluted in saline solution containing 300 microCi of 3Hcholine. Twenty-four rats (18 experimental, six control) were killed on day 21, four viable fetuses were removed from each, and the four pairs of fetal lungs from each rat were pooled. Phospholipids were extracted and separated by thin-layer chromatography. Incorporation of 3Hcholine represented amounts of newly induced pulmonary lecithin and sphingomyelin. Results were expressed in terms of percentage change from control. Betamethasone appeared to be the most potent, with a statistically significant greater effect at the 6.4 mg/kg dosage level (two-factor analysis of variance, p = 0.03). There appeared to be a suppressive effect of all corticosteroids at the 12.8 mg/kg dosage level. If similar responses were observed in primates, the results would suggest that higher dosage levels of betamethasone (up to four times the presently recommended dose of approximately 0.34 mg/kg) might be more efficacious.
Subject(s)
Betamethasone/administration & dosage , Dexamethasone/administration & dosage , Lung/embryology , Prednisolone/administration & dosage , Pulmonary Surfactants/biosynthesis , Animals , Female , Injections, Intraperitoneal , Phosphatidylcholines/biosynthesis , Pregnancy , Rats , Sphingomyelins/biosynthesisABSTRACT
The topical application of the promoter, 12-O-tetradecanoyl-13-acetate, on the shaved backs of mice was attended by a striking increase in the PGE concentration within epidermis as early as 1 h later. This increase peaked at 24 h but the prostaglandin value remained elevated for at least 48 h. PGF, on the other hand, showed only a modest increase in epidermis with a maximum at 12 h. By 48 h, the PGF concentration returned to normal.
Subject(s)
Phorbols/pharmacology , Prostaglandins E/biosynthesis , Prostaglandins F/biosynthesis , Skin/drug effects , Tetradecanoylphorbol Acetate/pharmacology , Administration, Topical , Animals , Male , Mice , Neoplasms, Experimental/etiology , Prostaglandins E/physiology , Skin/metabolism , Skin Neoplasms/etiology , Tetradecanoylphorbol Acetate/administration & dosage , Time FactorsABSTRACT
Syrian golden hamsters were placed on a control or vitamin A-deficient diet. When their serum vitamin A content was significantly reduced, i.e., to less than 10% of controls, the hamsters were killed and lung aryl hydrocarbon hydroxylase activity and metabolism of benzo(a)pyrene were determined. The benzo(a)pyrene metabolite profile was similar with control and A-deficient systems, and only few quantitative differences were noted. Addition of beta-retinyl acetate to the in vitro incubations did not substantially affect benzo(a)pyrene metabolism.
Subject(s)
Benzopyrenes/metabolism , Lung/metabolism , Vitamin A Deficiency/metabolism , Animals , Aryl Hydrocarbon Hydroxylases/metabolism , Cricetinae , Diterpenes , In Vitro Techniques , Male , Mesocricetus , Microsomes/metabolism , Retinyl Esters , Vitamin A/analogs & derivatives , Vitamin A/pharmacologyABSTRACT
A sensitive, highly reproducible method for tissue tocopherol analysis that combines saponification in the presence of large nmount of ascorbic acid to remove interfering substances, extraction fo the nonsponifiable lipids with hexane, and fluorometric measurement of the tocopherol is presented. The nonsaponifiable lipids phase contained only one fluorochrome in the 290 am excitation and 330 nm emission range, and it was identified as tocopherol by thin layer and column chromatography. Column chromatography of the hexane extract of a saponified, 14C-tocopherolspiked microsomal fraction showed that no measurable oxidation to tocopherylquinone had occurred. The flurometric method for tocopherol analysis was applied to homogenates and subcellular fractions from rat liver, kidney, lung, and heart and red blood cells. The heavy mitochondrial and microsomal fractions had the highest subcellular concentrations of tocopherol.
