Related Experiment Videos
Effects of long-term treatment with trandolapril on augmented vasoconstriction in rats with chronic heart failure
1Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Insights
Angiotensin I-converting enzyme (ACE) inhibitors reversed impaired vascular function in rats with chronic heart failure (CHF). Long-term ACE inhibitor treatment improved contractile properties in vessels, suggesting vascular beds are key therapeutic sites for CHF.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Vascular Biology
Background:
- Chronic heart failure (CHF) is associated with impaired vascular function.
- The precise effects of angiotensin I-converting enzyme (ACE) inhibitors on vascular function in CHF remain unclear.
Purpose of the Study:
- To investigate the impact of long-term ACE inhibitor treatment on altered vascular contractile properties in a rat model of CHF.
Main Methods:
- Rats underwent coronary artery ligation to induce CHF.
- Isometric tension development was assessed in thoracic aorta, pulmonary artery, and mesenteric artery segments.
- Contractile responses to norepinephrine, prostaglandin F2 alpha, and angiotensin II were measured with and without endothelium.
- Trandolapril was administered orally from week 2 to 12 post-operation.
Main Results:
- CHF rats exhibited augmented contractile responses to norepinephrine and prostaglandin F2 alpha in endothelium-intact aorta and pulmonary artery.
- Angiotensin II response was augmented in endothelium-denuded mesenteric arteries of CHF rats.
- Trandolapril treatment normalized these augmented contractile responses in CHF rats.
Conclusions:
- ACE inhibitors can reverse abnormal vascular function in CHF.
- Vascular beds represent potential sites of action for ACE inhibitors in CHF therapy.
Background:
Despite the clinical relevance of angiotensin I-converting enzyme (ACE) inhibitors, their effects on impaired vascular function in patients and animals with chronic heart failure (CHF) have not been fully understood. This study was undertaken to determine whether long-term treatment with an ACE inhibitor improved the altered contractile properties of vessels from rats with CHF.
Methods And Results:
Twelve weeks after coronary artery ligation, the rats were sacrificed and the isometric tension development of thoracic aorta, pulmonary artery, and mesenteric artery with and without endothelium was examined. Contractile responses to norepinephrine and prostaglandin F2 alpha were augmented in endothelium-intact, but not in endothelium-denuded, thoracic aorta and pulmonary artery segments of the rat with CHF. The contractile response to angiotensin II was augmented in endothelium-denuded mesenteric artery segments of the rat with CHF, which was attenuated by indomethacin or diclofenac sodium but not by bunazosin. Trandolapril (3 mg/kg/d) was administered orally from the 2nd to 12th week after the operation. Treatment with trandolapril reversed the augmented contractile response of the rat with CHF to norepinephrine, prostaglandin F2 alpha, and angiotensin II almost to the levels in the sham-operated rat.
Conclusions:
The results demonstrate that an ACE inhibitor is capable of reversing altered vascular function in the rat with CHF, suggesting that vascular beds are possible sites of action for ACE inhibitors in the therapy for CHF.