Impaired vascular smooth muscle nitric oxide-dependent relaxation in human coronary arteries from "transplanted heart vasculopathy".
The long-term prognosis after heart transplant is mainly determined by the development of transplant vasculopathy. The pathogenic mechanism of transplant vasculopathy remain uncertain, although endothelial dysfunction has been postulated. The objective of this work is to evaluate the smooth muscle and endothelium nitric oxide relaxing mechanisms in coronary arteries from patients with transplant vasculopathy. We studied human coronary arteries obtained from heart transplant surgery specimens of patients with heart transplant vasculopathy, ischaemic cardiopathy or dilated cardiomyopathy. Rings from the coronary arteries were mounted on stainless steel hooks in 40 ml organ bath. The tissues were contracted with phenylephrine (approx. ED 80-90) and concentration-response curves were performed with glyceryltrinitrate and acetylcholine. Glyceryltrinitrate relaxed arterial rings from patients with dilated cardiomyopathy and ischaemic cardiopathy. Arterial rings from patients with heart transplant vasculopathy showed a lower response to glyceryltrinitrate. Acetylcholine induced dilatation of coronary arteries from dilated cardiomyopathy but increased the tension in coronary rings from heart transplant vasculopathy and inschaemic cardiopathy. In conclusion, there is a lower response to glyceryltrinitrate and a paradoxical response to acetylcholine in arteries from patients with transplant vasculopathy. The response to glyceryltrinitrate may be a meaningful tool in the early diagnosis of transplant vasculopathy.
Salas
E
E
Division of Cardiology, University Hospital M. Valdecilla, University of Cantabria, Santander, Spain.
Amado
J A
JA
Sánchez de Vega
M J
MJ
Poveda
J J
JJ
Berrazueta
J R
JR
D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D001161:Arteriosclerosis / Q000473:pathology; D002311:Cardiomyopathy, Dilated / Q000473:pathology; D003331:Coronary Vessels / Q000502:physiology*; D016027:Heart Transplantation / Q000009:adverse effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D005996:Nitroglycerin; D000109:Acetylcholine