Drugs online research references









J Cardiovasc Pharmacol. 1990;16 Suppl 4:S42-9.
The proliferative response to vascular injury is suppressed by angiotensin-converting enzyme inhibition.

Powell JS, Muller RK, Rouge M, Kuhn H, Hefti F, Baumgartner HR.

F. Hoffmann-La Roche Ltd., Basel, Switzerland.

Smooth muscle cell (SMC) proliferation and formation of extracellular matrix in the intima of muscular arteries are major processes that can lead to vascular stenosis in arteriosclerosis or after coronary angioplasty. These processes are also seen in the proliferative response to balloon catheter-induced vascular injury of the rat carotid artery, and result in marked neointima formation by 14 days after catheterization. We have shown recently that the angiotensin-converting enzyme (ACE) inhibitor cilazapril strongly suppressed this development of neointima. In this report, we show that the beneficial effects on neointima formation persist for at least 8 weeks after stopping treatment with cilazapril, and that continuous treatment may have additional inhibitory effects during the late phases of vascular remodeling after injury. To investigate further the possible mechanisms, we examined several vasoactive compounds in this model. Another ACE inhibitor of a different chemical class, captopril, reduced neointima formation as strongly as cilazapril (67 and 78%, respectively), but the calcium antagonist verapamil was not active as an inhibitor of neointima formation, despite similar lowering of blood pressure. Hydralazine and a new calcium antagonist, Ro 40-5967, partially suppressed neointima formation (36%, p less than 0.005 and 33%, p less than 0.05, respectively). In vitro, neither cilazapril nor its active metabolite, cilazaprilate, had any effect on SMC proliferation in response to serum or PDGF. To characterize further the role of angiotensin II (Ang II), we tested in cell culture the effects of Ang II and cilazaprilate on mRNA levels of several proteins potentially involved in regulating the SMC response.(ABSTRACT TRUNCATED AT 250 WORDS)

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1705627&dopt=Abstract




J Endocrinol. 1989 Aug;122(2):499-507.
[3H]angiotensin II binding to basolateral membranes from rat proximal renal tubule: effect of sodium intake and captopril.

Lewis NP, Ferguson DR.

Department of Pharmacology, University of Cambridge.

Basolateral membranes were prepared from rat renal cortex by density gradient centrifugation. Their purity was confirmed by electron microscopy and by marker enzyme enrichment. The basolateral membrane preparation was shown to be derived predominantly from the proximal renal tubule by measurement of hormone-stimulated adenylate cyclase; marked stimulation of adenylate cyclase was found with parathyroid hormone, but not with isoprenaline, antidiuretic hormone or calcitonin. A single class of specific high-affinity [3H]angiotensin II-binding site was identified in the basolateral membrane preparation which, after correction of results for tracer degradation, showed equilibrium dissociation constant of 0.23 nmol/l and binding site concentration of 485.8 fmol/mg protein. Binding sites for [3H]angiotensin II were measured in basolateral membranes prepared from rats fed diets with a low, normal or high sodium content. A trend of increased binding site density with reduced sodium intake was found which did not reach statistical significance. No effect on affinity was demonstrated. Treatment of rats on a low-sodium diet with captopril (500 mg/l drinking water) caused a significant reduction in binding site density; no effect on affinity was demonstrated. These findings suggest that the density of angiotensin II receptors at this site is altered by the activity of the renin-angiotensin system.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2549161&dopt=Abstract




Arch Dis Child. 1989 Feb;64(2):229-34.
The captopril test: an aid to investigation of hypertension.

Daman Willems CE, Shah V, Uchiyama M, Dillon MJ.

Renal Unit, Hospital for Sick Children, London.

Twenty three children aged from 5 to 16 with mild to moderate hypertension were investigated using the orally active angiotensin converting enzyme inhibitor captopril. Falls in both systolic and diastolic blood pressure after a single dose of captopril were significantly correlated with initial plasma renin activity. In addition, some information about the aetiology of hypertension was deduced from the renin response to captopril. The blood pressure response to captopril is a useful screening test for renin dependent hypertension in childhood.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2649017&dopt=Abstract













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