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Functional and reactive hyperemia are unaltered by homocysteine in conscious dogs
Insights
L-homocysteine thiolactone (L-HCTL) did not affect myocardial function or blood flow responses, despite increasing homocysteine and S-adenosylhomocysteine levels. This suggests adenosine may not be a key regulator of coronary flow.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
Background:
- Adenosine plays a role in regulating myocardial blood flow.
- Homocysteine metabolism can influence cardiovascular function.
Purpose of the Study:
- To investigate if L-homocysteine thiolactone (L-HCTL) modulates myocardial functional and reactive hyperemia.
- To test the hypothesis that L-HCTL, via S-adenosylhomocysteine formation, impacts coronary circulation.
Main Methods:
- Studied reactive hyperemia (10-sec and diastolic occlusions) and functional hyperemia (ventricular extra-activations) in dogs.
- Administered L-HCTL (40 mg/kg) and measured plasma homocysteine and myocardial S-adenosylhomocysteine levels.
Main Results:
- L-HCTL administration significantly increased plasma homocysteine (75-fold) and myocardial S-adenosylhomocysteine (26-fold).
- Despite biochemical changes, L-HCTL did not alter myocardial functional or reactive hyperemic responses.
Conclusions:
- L-homocysteine thiolactone does not appear to modulate myocardial functional or reactive hyperemic responses in this model.
- Adenosine may not be a critical regulator of coronary blood flow, or L-HCTL does not affect its myocardial release.
Abstract:
The purpose of this study was to test the hypothesis that L-homocysteine thiolactone (L-HCTL), through its reaction with adenosine to form S-adenosylhomocysteine, may modulate myocardial functional and reactive hyperemic responses. Reactive hyperemic responses to 10-sec occlusions or 400-msec diastolic occlusions of the circumflex coronary artery and functional hyperemic responses to ventricular extra-activations were studied in a chronic heart-blocked dog preparation during a control period and following L-HCTL (40 mg/kg). In two additional dogs multiple venous blood samples and left ventricular myocardial biopsies were obtained following L-HCTL to measure changes in plasma homocysteine and tissue S-adenosylhomocysteine. Despite a 75-fold increase in peak plasma homocysteine and a 26-fold increase in tissue S-adenosylhomocysteine, L-HCTL did not alter myocardial functional and reactive hyperemic responses. The rapid increase in myocardial S-adenosylhomocysteine confirmed cellular entry of homocysteine and its reaction with endogenous adenosine. The failure of L-HCTL to alter functional and reactive hyperemic responses suggests that either such treatment does not affect myocardial release of adenosine or that adenosine is not an important regulator of coronary flow.