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Hypertension exacerbates the effect of hypercholesterolemia on the myocardial microvasculature
Martin Rodriguez-Porcel1, Amir Lerman, Joerg Herrmann
1Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
Insights
Hypertension (HT) worsens hypercholesterolemia (HC)-induced heart dysfunction by increasing oxidative stress. Antioxidant vitamins improved vascular responses in combined HC and HT, suggesting a therapeutic target for preventing cardiac events.
Area of Science:
- Cardiovascular Research
- Atherosclerosis
- Oxidative Stress
Background:
- Hypercholesterolemia (HC) and hypertension (HT) are key risk factors for atherosclerotic heart disease.
- Co-existing HC and HT increase cardiac event incidence.
- The impact of HT on HC-induced myocardial vascular dysfunction is not fully understood.
Purpose of the Study:
- To investigate how renovascular HT superimposed on diet-induced HC affects myocardial perfusion and microvascular permeability.
- To assess the role of systemic and myocardial oxidative stress in this interaction.
- To determine if antioxidant supplementation can mitigate these effects.
Main Methods:
- Studied pigs with diet-induced HC and superimposed renovascular HT (HC+HT).
- Assessed myocardial perfusion and microvascular permeability using electron-beam computed tomography during cardiac challenge (adenosine, dobutamine).
- Evaluated systemic and myocardial oxidative stress markers, including LDL oxidizability, antioxidant levels, and radical-scavenger activity.
Main Results:
- HC+HT significantly blunted myocardial perfusion response to adenosine and dobutamine compared to HC or HT alone.
- HC+HT showed increased microvascular permeability and failed to decrease vascular resistance during challenge.
- Elevated systemic and myocardial oxidative stress, with decreased antioxidant defenses, were observed in HC+HT, and antioxidant vitamin supplementation improved vascular function.
Conclusions:
- Hypertension amplifies HC-induced myocardial microvascular dysfunction.
- Increased oxidative stress plays a significant role in the combined effects of HC and HT on the heart.
- These findings suggest a mechanism for increased cardiac events in patients with co-existing HC and HT and highlight the potential benefit of antioxidant therapies.
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.