Improvement of EDHF by chronic ACE inhibition declines rapidly after withdrawal in rats with myocardial infarction.

Abstract

Heart failure after myocardial infarction (MI) is associated with endothelial dysfunction. There is conflicting evidence on the exact nature of this endothelial dysfunction and how endothelium-dependent vasodilation is affected by angiotensin-converting enzyme inhibitor (ACE-I) therapy. Furthermore, consequences of acute ACE-I withdrawal are largely unknown. Therefore, we studied the contribution of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to the effects of ACE-I therapy and its withdrawal on endothelial function in MI rats. Rats were subjected to coronary ligation to induce MI and were assigned to quinapril or vehicle from 2 weeks to 8 months post-MI. In parallel, MI rats treated for 14 months with quinapril were subjected to treatment withdrawal for 0, 4, and 6 weeks. Acetylcholine (ACh)-induced relaxation and underlying endothelium-derived mediators were studied in isolated aortic rings. Long-term quinapril (8 months) resulted in markedly improved endothelium-dependent vasodilation in rats with myocardial infarction, which could be attributed to marked improvement in non-NO/prostanoid-mediated relaxation (ie, EDHF). After 14 months of follow-up, maximum vasodilation was still preserved by quinapril. Withdrawal after 14 months of treatment caused significantly impaired ACh-induced EDHF-mediated relaxation within 4 weeks. A marked reduction in EDHF-mediated relaxation caused this impairment. NO-mediated relaxation was unaffected. These findings highlight the importance of EDHF impairment in development of endothelial dysfunction after myocardial infarction and the possibility of improving EDHF-mediated vasodilation with chronic ACE inhibitor therapy. In addition, withdrawal of chronic ACE inhibition after MI should be considered carefully, as profound endothelial dysfunction may develop rapidly.

• Authors: Bart Westendorp, Regien G Schoemaker, Wiek H van Gilst, Hendrik Buikema
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 46 Issue 6 Pg. 766-72 (Dec 2005) ISSN: 0160-2446 [Print] United States
• PMID: 16306800 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Biological Factors
• Tetrahydroisoquinolines
• endothelium-dependent hyperpolarization factor
• Aldosterone
• Acetylcholine
• Quinapril

Topics

• Acetylcholine (pharmacology)
• Aldosterone (blood)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Animals
• Biological Factors (physiology)
• Endothelium, Vascular (physiology)
• Male
• Myocardial Infarction (drug therapy, physiopathology)
• Quinapril
• Rats
• Rats, Sprague-Dawley
• Tetrahydroisoquinolines (pharmacology, therapeutic use)
• Vasodilation (drug effects)