title: Hypertension exacerbates the effect of hypercholesterolemia on the myocardial microvasculature.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Rodriguez-Porcel
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.forename: Joerg
authors.initials: J
authors.lastname: Herrmann
authors.forename: Robert S
authors.initials: RS
authors.lastname: Schwartz
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
authors.forename: Mario
authors.initials: M
authors.lastname: Condorelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Napoli
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D000241:Adenosine; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004280:Dobutamine; D005260:Female; D006937:Hypercholesterolemia / Q000150:complications*; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D010084:Oxidation-Reduction; D012039:Regional Blood Flow; D013552:Swine; D014057:Tomography, X-Ray Computed; D014801:Vitamin A / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D014801:Vitamin A; D014810:Vitamin E; D004280:Dobutamine; D000241:Adenosine