Document Detail

Hypertension exacerbates the effect of hypercholesterolemia on the myocardial microvasculature.
MedLine Citation:
PMID:  12667964     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Hypercholesterolemia (HC) and hypertension (HT) are both major risk factors for the development and progression of atherosclerotic heart disease, and their co-existence has been associated with an increased incidence of cardiac events in clinical studies. HC and HT are individually associated with abnormal myocardial vascular function, but whether HT exacerbates the HC-induced myocardial vascular dysfunction remains unclear. METHODS: We studied in pigs the effect of renovascular HT superimposed on diet-induced HC (HC+HT) on myocardial perfusion and microvascular permeability in vivo (using electron-beam computed tomography) in response to cardiac challenge (i.v. adenosine and dobutamine). The involvement of systemic and myocardial tissue oxidative stress in vitro was assessed by oxidizability of LDL, levels of endogenous antioxidants, and tissue activities of radical-scavenger systems. RESULTS: While in normal animals myocardial perfusion increased in response to i.v. adenosine (+36+/-13%, P<0.05), in HC and HT alone the increase was blunted. In HC+HT myocardial perfusion response was further attenuated and significantly lower than normal, and myocardial vascular resistance failed to decrease (+7.6+/-8.8 vs. -21.0+/-5.8%, P=0.02 versus normal). HC+HT also showed blunted response to dobutamine, and augmented increases in microvascular permeability in vivo. These functional abnormalities were associated with increased systemic and myocardial tissue oxidative stress compared to HC or HT alone, and a synergistic decrease in endogenous antioxidant defenses in myocardial tissue. Furthermore, chronic antioxidant vitamin supplementation in combined HC and HT improved myocardial vascular responses. CONCLUSION: HT amplifies the HC-induced myocardial microvascular dysfunction in vivo and increased oxidative stress in vitro. These alterations may potentially play a role in the increased incidence of cardiac events observed when HC and HT co-exist.
Martin Rodriguez-Porcel; Amir Lerman; Joerg Herrmann; Robert S Schwartz; Tatsuya Sawamura; Mario Condorelli; Claudio Napoli; Lilach O Lerman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cardiovascular research     Volume:  58     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-01     Completed Date:  2003-06-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  213-21     Citation Subset:  IM    
Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
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MeSH Terms
Adenosine / diagnostic use*
Antioxidants / therapeutic use
Capillary Permeability / drug effects
Coronary Circulation / drug effects*
Dobutamine / diagnostic use*
Hypercholesterolemia / complications*
Hypertension / blood*,  drug therapy
Regional Blood Flow
Tomography, X-Ray Computed
Vitamin A / therapeutic use
Vitamin E / therapeutic use
Grant Support
Reg. No./Substance:
0/Antioxidants; 11103-57-4/Vitamin A; 1406-18-4/Vitamin E; 34368-04-2/Dobutamine; 58-61-7/Adenosine

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