Drugs online research references
Gen Pharmacol. 1991;22(5):923-7.
The effect of doxazosin, urapidil and indoramin pretreatment on fever produced by E. coli lipopolysaccharide in rabbits.
Gagalo I, Szreder Z.
Department of Pharmacology, Medical Academy, Gdansk, Poland.
1. Thermal responses to i.v. administration of doxazosin (0.75 or 1.50 mg/kg), urapidil (5.0 or 10.0 mg/kg), or indoramin (0.75 or 1.50 mg/kg) were investigated in febrile rabbits (treated with Escherichia coli lipopolysaccharide) at an ambient temperature of 19 +/- 1 degree C. 2. All these alpha 1-adrenoceptor blockers produced statistically significant antipyresis which developed as a result of inhibition of metabolic heat production and/or stimulation of heat elimination from the ear skin area or respiratory tract. 3. It appears that the antipyretic effect is a general feature of alpha 1-adrenergic receptor blockers. The possible mechanisms by which antipyresis is produced are being considered.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1684772&dopt=Abstract
Clin Exp Pharmacol Physiol. 1991 Nov;18(11):775-88.
Effects of adrenoreceptor antagonists and agonists on clearance of emulsion models of triacylglycerol-rich lipoproteins from plasma in rats.
Mackintosh VS, Elsegood CL, Redgrave TG.
Department of Physiology, University of Western Australia, Nedlands.
1. We previously found that adrenaline and noradrenaline exert essentially opposite effects on clearance from plasma of chylomicron-like emulsions injected intravenously in rats, suggesting mechanisms that may be implicated in the atherogenic effects of chronic stress and hypertension and conversely in the protective effect of regular exercise. 2. The mechanisms underlying the effects of adrenaline and noradrenaline have now been investigated. Chronic adrenergic blockade with either the alpha 1-receptor antagonist doxazosin or the beta-receptor antagonist propranolol slowed the clearance of labelled emulsion lipids from plasma of normal Wistar rats. The results with doxazosin were unexpected in view of its capacity to decrease plasma triglycerides in patients. 3. In spontaneously hypertensive rats (SHR) the clearance of triolein (TO) was very slow compared with normal Wistar rats. Emulsion TO clearance provides a measure of lipolysis by lipoprotein lipase, and a defect in clearance indicates either defective enzyme action or poor perfusion of capillary beds rich in enzyme. Defective enzyme activity in SHR was excluded, suggesting redistribution of blood flow away from skeletal muscle and adipose tissue. In SHR the TO clearance from injected chylomicron-like emulsions was improved by blockade with doxazosin compared with control untreated SHR. 4. The beta 2-adrenoreceptor agonist Fenoterol was infused intravenously during clearance of an injected lipid emulsion. Clearance of radiolabelled cholesteryl oleate (CO) was clearly slowed while there was a lesser reduction of TO clearance rate. Emulsion CO clearance provides a measure of the uptake of lipoprotein remnants by the liver, and a defect in clearance of CO indicates either defective ligand (apolipoprotein E)-receptor interaction or decreased perfusion of the splanchnic bed. Isoprenaline, a non-selective beta-adrenergic agonist, gave similar results. Both compounds reduced mean arterial pressure by about 20-40 mm Hg at the doses employed, indicating that the beta 1 (cardiac) effect of the isoprenaline was insufficient to offset its vasodilatatory effect on skeletal muscle arterioles (beta 2). 5. The alpha-agonist phenylephrine, at a dose which moderately raised mean arterial pressure, slowed clearance of both TO and CO for the first 12 min after injection of emulsion but at later time points clearances caught up with the controls. 6. Administration of a mixture of isoprenaline and phenylephrine produced definite enhancement of both TO clearance and CO clearance. The effect of the mixture was opposite to the effects of of either agonist alone, demonstrating clearly that direct effects on lipoprotein lipase activity or receptor mediated processes were not involved.(ABSTRACT TRUNCATED AT 400 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1685947&dopt=Abstract
Atherosclerosis. 1991 Nov;91(1-2):35-49.
Doxazosin and cholestyramine similarly decrease fatty streak formation in the aortic arch of hyperlipidemic hamsters.
Kowala MC, Nunnari JJ, Durham SK, Nicolosi RJ.
Department of Clinical Sciences, University of Lowell, MA 01854.
The effect of doxazosin, an alpha-1 adrenergic inhibitor, on atherosclerosis was determined in hyperlipidemic hamsters. Control hamsters fed chow plus 0.05% cholesterol and 10% coconut oil were compared to chow baseline animals, and to those receiving either 10 mg/kg/day doxazosin, or 245 mg/kg/day cholestyramine in the atherogenic diet. During 8 weeks of treatment, plasma lipids, mean arterial pressure (MAP) and heart rate (HR) were measured, then the ascending aortic arch was examined en face. Numbers of subendothelial macrophage-foam cells/mm2 and their average size (microns 2) were determined, and Oil red O staining (micrograms ORO/mm2) was quantitated to estimate lipid accumulation. Ultracentrifugation of control plasma demonstrate that low density lipoprotein (LDL) carried most of the cholesterol, and very low density lipoprotein (VLDL) was rich in triglycerides. Compared to controls, doxazosin and cholestyramine similarly decreased plasma total and LDL plus VLDL cholesterols, and total triglycerides on average by 46%, 61% and 45% respectively. High density lipoprotein cholesterol was unchanged. Doxazosin also reduced MAP by 18% without affecting HR. In all hamsters, foam cells and lipid accumulated in a lesion-prone area characterized by elevated endothelial cell density, and a thick intima of basement membrane-like material layered over "pads" of smooth muscle cells. Compared to controls, doxazosin and cholestyramine uniformly reduced the number of foam cells/mm2, foam cell size and ORO staining on average by 66%, 29% and 56%, respectively. We conclude that doxazosin decreases plasma lipids and inhibits the development of the fatty streak to a similar level as cholestyramine treatment.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1687433&dopt=Abstract
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