What is the plasma cofactor required by diuretics for direct vascular relaxant effect in vitro?
OBJECTIVE
To determine the plasma cofactor which is required by diuretics (hydrochlorothiazide, chlorthalidone, indapamide, and furosemide) for direct vasorelaxant effects in vitro.


METHODS
A randomized, double-blind, vehicle-control design was used to avoid experimenter bias.


METHODS
We plotted concentration-response curves for responses to hydrochlorothiazide, chlorthalidone, indapamide, and furosemide of male Wistar rat aortic rings in the presence of different bath solutions containing various plasma factors.


RESULTS
Plasma was found both to make possible and facilitate the vasodilator action of the diuretics tested by an action on the membrane and to decrease the action by binding the diuretics. The diuretics retained their vasorelaxant properties in Krebs solution alone, 30 min after having been incubated in a 50:50 solution of Krebs solution and plasma for 1 h. All four diuretics exerted significant vasorelaxant actions in Krebs solution-plasma, Krebs solution-serum, and Krebs solution plus human or bovine albumin (40 g/l) media. No vasorelaxant action was found in Krebs solution alone, Krebs solution plus denatured plasma, Krebs solution plus egg albumin, and Krebs solution plus insulin.


CONCLUSIONS
Albumin is the main cofactor required by the diuretics tested for direct relaxant action in vitro, and these findings may explain some of the contradictory evidence concerning this action in the literature.
Abrahams
Z
Z
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
Pang
M Y
MY
Lam
E K
EK
Wright
J M
JM
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D001581:Benzothiadiazines; D001665:Binding Sites; D004232:Diuretics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D010949:Plasma; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000494:pharmacology; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*; D013449:Sulfonamides; D014664:Vasodilation / Q000187:drug effects*
D001581:Benzothiadiazines; D004232:Diuretics; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D012709:Serum Albumin; D049993:Sodium Chloride Symporter Inhibitors; D013449:Sulfonamides