Differential effects of sodium nitroprusside and hydralazine in a rat model of topical FeCl3-induced carotid artery thrombosis.
BACKGROUND
In the rat model of topical ferric chloride-induced carotid artery thrombosis, a transient blood flow velocity (VEL) increase is observed immediately following ferric chloride application. The immediacy of the response suggested vasoconstriction, as thrombotic narrowing of the vessel lumen was hypothesized to be too slow to account for the rapidity of the response.


METHODS
To explore this phenomenon, the effects of two mechanistically distinct vasodilators, sodium nitroprusside (SNP) and hydralazine (HYD), on velocity increase, ex vivo platelet aggregation and thrombosis, were assessed in the rat ferric chloride-induced thrombosis model.


RESULTS
Sodium nitroprusside (10, 30 and 50 microg/kg/min i.v.) and hydralazine (0.1, 0.3 and 1.0 mg/kg/min i.v.) reduced the mean arterial pressure with the higher dose regimens eliciting equivalent hypotensive effects. Both sodium nitroprusside and hydralazine blunted the initial velocity increase, but only sodium nitroprusside significantly reduced the incidence of thrombotic occlusion. No differences in ex vivo platelet aggregation responses to adenosine diphosphate (ADP), collagen (COLL) and arachidonic acid (AA) were observed between the sodium nitroprusside and hydralazine treatment groups. However, platelet aggregation response to thrombin was significantly reduced in the 50 microg/kg/min i.v. sodium nitroprusside compared to the 1.0 mg/kg/min i.v. hydralazine and vehicle groups.


CONCLUSIONS
Inhibition of the initial velocity increase by two mechanistically distinct vasodilators, and the dissociation between this velocity change and antithrombotic efficacy, support the hypothesis that the early velocity increase results from a change in vascular tone rather than due to enhanced platelet activation and thrombus formation. Inhibition of thrombin-induced platelet activation may contribute to the antithrombotic actions of sodium nitroprusside in this preparation.
Robinson
Mary A
MA
Department of Pharmacology, Merck Research Laboratories, West Point, PA, USA.
Welsh
Denise C
DC
Bickel
Denise J
DJ
Lynch
Joseph J
JJ
Lyle
Elizabeth A
EA
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002341:Carotid Artery Thrombosis / Q000139:chemically induced / Q000188:drug therapy*; D002712:Chlorides; D004195:Disease Models, Animal; D005290:Ferric Compounds; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D009599:Nitroprusside / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000627:therapeutic use*
D002712:Chlorides; D005290:Ferric Compounds; D014665:Vasodilator Agents; D009599:Nitroprusside; D006830:Hydralazine; C024555:ferric chloride