[Flow-dependent vasodilation. Pharmacology and physiopathology].
The phenomenon of flow-dependent vasodilatation is characterised by the variations of vascular tone to changes in regional blood flow. Initially considered to be a purely myogenic reaction of a vessel to a change in blood flow in the microcirculation, it is now generally accepted that "flow-dependent" vasodilatation is closely related to the modulating properties of the vascular endothelium. Local chemical or mechanical destruction of the vascular endothelium abolishes any vasomotor response in that particular region to increased blood flow in that vessel (for example during a hyperemic response or after injection of papaverine), whereas the response to a substance directly relaxing the smooth muscle of the large arteries (such as nitroglycerine) remains unchanged. Bioassay methods have shown that the fundamental mechanism of flow dependence is the liberation of one or more relaxing factors (EDRF) from endothelial cells sensitive to variations in shear stress which accompany all changes in regional blood flow. From the pharmacological point of view, flow-dependent vasodilatation enables identification of several types of vasodilator drugs depending on whether the relaxation of vascular smooth muscle which follows their administration remains the same or not in the absence of concomitant changes in regional blood flow. The vasodilatation caused by calcium antagonists and potassium agonists is largely related to the phenomenon of flow-dependency whilst that induced by nitroglycerin is totally independent. Finally, from the physiopathological view-point, the clinical studies published in this domain show that blood pressure has little influence on flow-dependent vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Berdeaux
A
A
Laboratoire de pharmacologie, faculté de médecine Paris-Sud, Le Kremlin-Bicêtre.
Drieu La Rochelle
C
C
Gosgnach
M
M
Roupie
E
E
Richard
V
V
Giudicelli
J F
JF
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D012039:Regional Blood Flow; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009569:Nitric Oxide
La dilatation débit-dépendante. Aspects pharmacologiques et physiopathologiques.