Journal article
Altered vascular responses to platelets from hypercholesterolemic humans
Circulation research, Vol.72(4), pp.737-743
1993
DOI: 10.1161/01.RES.72.4.737
PMID: 8443865
Abstract
Activated platelets release potent vasoactive factors. Previous studies have focused on mechanisms by which vascular abnormalities lead to altered responses of atherosclerotic arteries. We tested the hypothesis that the activation of platelets from hypercholesterolemic humans produces abnormal vascular responses. Responses to intraluminal and abluminal activation of platelets from normal subjects and type II hypercholesterolemic patients (total cholesterol, 274 +/- 16 [mean +/- SEM] mg/dl) were examined in carotid arteries from normal rabbits perfused in vitro. Intraluminal activation of normal platelets produced pronounced dilatation of arteries preconstricted with phenylephrine. Vasodilator responses to intraluminal activation of platelets from hypercholesterolemic patients were greatly impaired. Vasodilator responses to platelets from hypercholesterolemic patients were not restored to normal by LY53,857 (10(-5) M), a 5-hydroxytryptamine2-serotonergic antagonist, by SQ29,548 (10(-5) M), a thromboxane A2/prostaglandin H2 receptor antagonist, or by apyrase (1.5 units/ml), an enzyme with ADPase activity. Abluminal activation of normal platelets produced modest constriction in quiescent arteries, and abluminal activation of platelets from hypercholesterolemic patients produced augmented vasoconstrictor responses. The major finding is that vasodilator responses to platelets from hypercholesterolemic patients are profoundly impaired, and vasoconstrictor responses to platelets from hypercholesterolemic patients are augmented. Mechanisms in addition to increased release of serotonin, thromboxane, and ADP appear to contribute to impaired vasodilator responses to hypercholesterolemic platelets. Thus, alteration of platelets by hypercholesterolemia, as well as altered vascular reactivity, may contribute to abnormal vascular responses in atherosclerosis.
Details
- Title: Subtitle
- Altered vascular responses to platelets from hypercholesterolemic humans
- Creators
- Sanjay Kaul - Univ. Iowa coll. medicine, cent. aging, dep. internal medicine pharmacology, Iowa City IA 52242, United StatesB. J WAACK - Univ. Iowa coll. medicine, cent. aging, dep. internal medicine pharmacology, Iowa City IA 52242, United StatesR. C PADGETT - Univ. Iowa coll. medicine, cent. aging, dep. internal medicine pharmacology, Iowa City IA 52242, United StatesR. M BROOKS - Univ. Iowa coll. medicine, cent. aging, dep. internal medicine pharmacology, Iowa City IA 52242, United StatesD. D HEISTAD - Univ. Iowa coll. medicine, cent. aging, dep. internal medicine pharmacology, Iowa City IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.72(4), pp.737-743
- Publisher
- Lippincott; Hagerstown, MD
- DOI
- 10.1161/01.RES.72.4.737
- PMID
- 8443865
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 1993
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040596402771
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