Serotonin blockade protects against early microvascular constriction following atherosclerotic plaque rupture.
Early microvascular constriction following atherosclerotic plaque rupture may be mediated via serotonin and/or endothelin-1. Atherosclerotic lesions in the rabbit hindlimb underwent plaque rupture, resulting in a rapid reduction of distal flow (7.1+/-0.7 ml/min pre-rupture versus 3.6+/-0.6 ml/min post-rupture, P<0.001) and a rise in distal microvascular resistance (10.5+/-0.9 mm Hg min/ml pre-rupture versus 23.5+/-3.5 mm Hg min/ml post-rupture, P=0.01). Distal microvascular resistance remained elevated following endothelin-1 receptor antagonism and control vehicle, but normalised after serotonin receptor antagonism with ritanserin (10.5+/-0.9 mm Hg min/ml pre-rupture versus 22.2+/-6.0 mm Hg min/ml post-endothelin-1 receptor antagonism [P<0.05] versus 21.6+/-6.2 mm Hg min/ml post-control vehicle [P<0.05] versus 11.6+/-2.0 mm Hg min/ml post-ritanserin [P=NS]). Early antagonism of serotonin receptors protects against distal microvascular constriction following atherosclerotic plaque rupture.
Taylor
Andrew J
AJ
Baker Heart Research Institute, Alfred Hospital, Commercial Road, Prahran, Melbourne 3181, Australia. andrew.taylor@baker.edu.au
Bobik
Alex
A
Berndt
Michael C
MC
Kannelakis
Peter
P
Jennings
Garry
G
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000187:drug effects; D004195:Disease Models, Animal; D007083:Iliac Artery / Q000187:drug effects / Q000502:physiology; D007189:Indans / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D044348:Receptors, Serotonin, 5-HT2 / Q000502:physiology; D016713:Ritanserin / Q000494:pharmacology* / Q000627:therapeutic use; D012421:Rupture / Q000188:drug therapy / Q000503:physiopathology; D058830:Serotonin 5-HT2 Receptor Antagonists; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D007189:Indans; D044348:Receptors, Serotonin, 5-HT2; D058830:Serotonin 5-HT2 Receptor Antagonists; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-; D016713:Ritanserin