Drugs online research references
Hypertension. 1985 Sep-Oct;7(5):797-803.
Effects of a specific and long-acting renin inhibitor in the marmoset.
Wood JM, Gulati N, Forgiarini P, Fuhrer W, Hofbauer KG.
Inhibition of renin was induced in conscious marmosets with CGP 29 287, Z-Arg-Arg-Pro-Phe-His-Sta-Ile-His-Lys (Boc)-OMe, a renin inhibitor with a prolonged duration of action. In vitro, CGP 29 287 is a potent inhibitor of primate plasma renin (inhibitory concentration, 50%: human = 1 X 10(-9) M; marmoset = 5 X 10(-9) M) and less potent against dog (2 X 10(-7) M) or rat (3 X 10(-5) M) plasma renin. CGP 29 287 is a weak inhibitor of other aspartic proteases such as porcine pepsin or bovine cathepsin D (inhibitory concentration, 50% = 4 X 10(-5) M). In furosemide-treated marmosets, CGP 29 287 lowered blood pressure and inhibited plasma renin activity during intravenous infusion and after intravenous bolus injection. The duration of action after intravenous injection was dose dependent and ranged from 1 hour after 0.1 mg/kg to more than 3 hours after 10 mg/kg. High doses of CGP 29 287 (100 mg/kg) were active after oral administration. In all experiments a close relation between inhibition of plasma renin activity and reduction of blood pressure was found. A maximum hypotensive response to CGP 29 287 was associated with complete inhibition of plasma renin activity, and the recovery of blood pressure was accompanied by recovery of plasma renin activity. The hypotensive effects of CGP 29 287 were smaller in untreated than in furosemide-treated marmosets. CGP 29 287 had no influence on blood pressure in marmosets after bilateral nephrectomy or after pretreatment with a converting enzyme inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3928488&dopt=Abstract
J Pharmacol Exp Ther. 1990 Jun;253(3):1184-8.
Furosemide acts on short loop of descending thin limb, but not on long loop.
Jung KY, Endou H.
Department of Pharmacology, Faculty of Medicine, University of Tokyo.
In order to elucidate the tubular sites of action of loop diuretics such as furosemide, bumetanide and ethacrynic-cysteine complex within isolated rat descending thin limbs, cellular ATP was measured by luciferin-luciferase technique. When short descending thin limbs of Henle's loop (SDL) were incubated in the absence of exogenous substrate at 37 degrees C, cellular ATP content was decreased in a time-dependent manner (up to 49% after 60 min). This ATP decrease, however, was retarded significantly in the presence of loop diuretics at 60 min. The mean percentage of change in ATP compared with the control for each loop diuretic in SDL was as follows: 10(-5) M furosemide, 178%; 10(-5) M bumetanide, 189%; and 10(-7) M ethacrynic-cysteine complex, 154%; respectively. To the contrary, cellular ATP in long descending thin limb of Henle's loop (LDL) was not changed by loop diuretics compared with the control. A similar protection against ATP depletion was observed in the medullary thick ascending limb of Henle's loop, in which the mean percentage was as follows: 10(-5) M furosemide, 163%; 10(-5) M bumetanide, 187%; and 10(-7) M ethacrynic-cysteine complex, 134%. Similarly to LDL, the cellular ATP did not change in outer medullary collecting tubule. From these results, we conclude that loop diuretics act on the isolated rat SDL, but not on LDL.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2359021&dopt=Abstract
Int J Clin Pharmacol Res. 1985;5(2):113-21.
Clinical pharmacology of loop diuretics: a comparative study.
Ansuini R, Pulido M, Pupita G, Gaggi S, Pupita F.
The authors performed two studies to clarify the characteristics, analogies and differences of three loop diuretics (furosemide, bumetanide and piretanide) aiming at more precise indications for their clinical use. In the first study, they compared bumetanide and piretanide by the method of compensated diuresis; in the second, they tested the three loop diuretics' efficacy in refractory ascites. The authors demonstrated that with the three substances analogous results were obtained when administered at equivalent doses and that only intensive diuresis was able to resolve refractory ascites.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=4018941&dopt=Abstract
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