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Effect of trandolapril on vascular responsiveness in cholesterol-fed rabbit-isolated arteries
1Department of Pharmacology, School of Medicine, Complutense University, 28040, Madrid, Spain.
Insights
Trandolapril, an angiotensin-converting enzyme (ACE) inhibitor, improved vascular function in hypercholesterolemic rabbits. The drug restored endothelium-dependent relaxation in arteries, suggesting a potential benefit against atherosclerosis.
Area of Science:
- Cardiovascular Pharmacology
- Vascular Biology
- Atherosclerosis Research
Background:
- Cardiovascular disorders are a leading cause of mortality globally.
- Hypercholesterolemia significantly impairs vascular function.
- Angiotensin-converting enzyme (ACE) inhibitors are crucial in managing cardiovascular diseases.
Purpose of the Study:
- To investigate the effects of trandolapril on vascular responsiveness in hypercholesterolemic rabbits.
- To assess trandolapril's impact on endothelium-dependent and independent relaxation.
- To determine if trandolapril mitigates vascular alterations associated with atherosclerosis.
Main Methods:
- Hypercholesterolemia was induced in rabbits using a cholesterol-enriched diet.
- Trandolapril was administered to a group of hypercholesterolemic rabbits.
- Vascular rings (aorta, coronary, mesenteric) were isolated and subjected to pharmacological challenge.
- Endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) relaxations were measured.
Main Results:
- Trandolapril did not alter plasma cholesterol, HDL, or LDL levels.
- Trandolapril significantly improved acetylcholine-induced relaxation in aortic and mesenteric arteries of hypercholesterolemic rabbits.
- Trandolapril enhanced serotonin-induced contraction in proximal coronary arteries.
- No significant differences in sodium nitroprusside-induced relaxation were observed.
Conclusions:
- Trandolapril effectively restores endothelium-dependent vascular relaxation in hypercholesterolemic conditions.
- The findings suggest trandolapril possesses beneficial vascular protective effects.
- Trandolapril may play a role in preventing atherosclerosis-related vascular damage.
Abstract:
According to the World Health Organisation, cardiovascular disorders are one of the main causes of morbi/mortality in the western world. The effect of trandolapril (0.3 mg kg(-1) day(-1)), a non-sulphydryl angiotensin-converting enzyme (ACE) inhibitor, on the vascular responsiveness in aorta isolated from hypercholesterolemic rabbits was examined. Three groups of rabbits (n=30) were used: Group 0 (control group); Group 1 (hypercholesterolemic group, 0.5% (wt/wt) cholesterol-enriched diet) and Group 2 (hypercholesterolemic+trandolapril 0.3 mg kg(-1) day(-1)). After 18 weeks of treatment, the rabbits were killed and the thoracic aorta, proximal coronary and mesenteric (5th branch) arteries were isolated, cleaned off and mounted in an organ bath. Trandolapril had no significant effect on plasma cholesterol, high density lipoprotein (HDL) or low density lipoprotein (LDL). Despite the lack of effect of the drug on the above-mentioned parameters, treatment with trandolapril improved endothelium-dependent relaxation induced by acetylcholine in aortic and mesenteric rings from hypercholesterolemic rabbits treated with trandolapril. The relaxation induced by 10(-5) M acetylcholine were 65.0+/-4.0%; 24. 0+/-9.4% (P<0.01, n=10) and 51.3+/-7.0% (P<0.01, n=10) in aortic rings from Groups 0, 1 and 2, respectively, and 50.0+/-12.0%; 10. 1+/-10.0% (P<0.01, n=10); 61.0+/-9.7% (P<0.01, n=10) in small mesenteric rings from Groups 0, 1 and 2, respectively. In addition, trandolapril treatment improved the increase in serotonin-induced contraction in proximal coronary arteries with respect to the hypercholesterolemic group. On the other hand, we did not find any differences among the group in endothelium-independent relaxation induced by sodium nitroprusside. These results provide evidence that trandolapril restores endothelium-dependent relaxation in hypercholesterolemic rabbit-isolated arteries. These data suggest that trandolapril might have beneficial action in the prevention of vascular alteration involved in atherosclerosis.