[Vascular pleiosynergism--a new concept?].

Vascularis pleioszinergizmus--egy uj fogalom?

Publisher: Akademiai Kiado Country of Publication: Hungary NLM ID: 0376412 Publication Model: Print Cited Medium: Print ISSN: 0030-6002 (Print) Linking ISSN: 00306002 NLM ISO Abbreviation: Orv Hetil Subsets: MEDLINE

Publication: 2007- : Budapest : Akademiai Kiado
Original Publication: Pest : Markusovszky Lajos

Amlodipine/*pharmacology ; Antihypertensive Agents/*pharmacology ; Calcium Channel Blockers/*pharmacology ; Carrier Proteins/*metabolism ; Cytokines/*metabolism ; Endothelium, Vascular/*drug effects ; Hypolipidemic Agents/*pharmacology ; Vascular Diseases/*drug therapy ; Vascular Diseases/*metabolism; Amlodipine/therapeutic use ; Antihypertensive Agents/therapeutic use ; Atorvastatin ; Calcium Channel Blockers/therapeutic use ; Carrier Proteins/drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cytokines/drug effects ; Endothelium, Vascular/metabolism ; Heptanoic Acids/pharmacology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Hypolipidemic Agents/therapeutic use ; Myocytes, Smooth Muscle/drug effects ; Nitric Oxide/biosynthesis ; Nitric Oxide Synthase Type III/drug effects ; Nitric Oxide Synthase Type III/metabolism ; Pyrroles/pharmacology ; Reactive Oxygen Species/antagonists & inhibitors

The coexistence of cardiovascular risk factors augments exponentially the relative risk value. Similarly, the parallel treatment of these risks proves multiplicative effectiveness. However, members of given drug classes show different capacity due to their variant main and other effects. Nowadays, among favorable "side" effects the pleoitropic form is in the focus of interest. In drugs with antiatherosclerotic outline the lipid lowering statins and the antihypertensive third generation calcium channel blocker amlodipin posses the widest pleiotropic profile. According to the newest molecular biological results both of them are able to enhance endothelial nitrogen-monoxid (NO) synthesis, to inhibit production of reactive oxide radicals and to reduce the migration and proliferation of smooth muscle cells, which mechanisms are independent from their main effects. Statins and amlodipin can increase the activity of eNOS by influencing the caveolin/eNOS complex. The presence of common targets in direct and indirect effects seems to be important in gaining greater efficacy. The valuable indirect therapeutical "cross reaction" can be delineated as pleiosynergism. The recent revisited results of ASCOT-LLA trial support in vitro observations. The difference in primary end points of atorvastatin/amlodipin versus atorvastatin/atenolol regimen against placebo was more than three times (3.3 x) greater in favour to amlodipin combination. The same benefits were seen in secondary end points. Because the capacity of the two schedules lowering blood pressure was very similar, the advantage can be based dominantly on the pleiosynergistic interaction between atorvastatin and amlodipin.

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0 (Antihypertensive Agents)
0 (Calcium Channel Blockers)
0 (Carrier Proteins)
0 (Cytokines)
0 (Heptanoic Acids)
0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
0 (Hypolipidemic Agents)
0 (Pyrroles)
0 (Reactive Oxygen Species)
134034-50-7 (pleiotrophin)
1J444QC288 (Amlodipine)
31C4KY9ESH (Nitric Oxide)
A0JWA85V8F (Atorvastatin)
EC 1.14.13.39 (Nitric Oxide Synthase Type III)

Date Created: 20061124 Date Completed: 20070420 Latest Revision: 20181201

20231215

17120687