Coronary vasodilation induced by intracoronary enalaprilat: an argument for the role of a local renin-angiotensin system in patients with dilated cardiomyopathy.
Although indicated by several experimental studies, the presence of a renin-angiotensin system has not been demonstrated in the human heart. The influence of a local renin-angiotensin system on the coronary vessels may be difficult to establish after oral or intravenous administration of an angiotensin converting-enzyme inhibitor, since coronary blood flow depends greatly on the loading conditions of the left ventricle. To avoid such a situation, our study consisted in a direct bilateral intracoronary infusion of enalaprilat in patients with dilated cardiomyopathy and normal coronary arteries (mean ejection fraction = 32 +/- 11%, n = 12). This intracoronary infusion (0.05 mg min-1, 1 ml min-1 in each coronary artery) resulted in no significant change of the systemic resistances (20.6 +/- 5.6 to 22.0 +/- 5.1 mmHg l-1 min), rate-pressure product (10,974 +/- 2630 to 10,214 +/- 2486) or myocardial oxygen consumption (21.08 +/- 6.37 to 22.10 +/- 6.42 ml min-1). Despite these steady haemodynamic conditions, intracoronary enalaprilat provoked a significant elevation of coronary sinus blood flow (181 +/- 73 to 214 +/- 79 ml min-1, P less than 0.001) with a reduction of coronary resistance (0.51 +/- 0.17 to 0.41 +/- 0.15 mmHg ml-1 min, P less than 0.001), and no significant alteration in plasma renin activity or plasma aldosterone. The results of this intracoronary infusion of enalaprilat demonstrate that this angiotensin converting-enzyme inhibitor has significant coronary vasodilator properties, which can be evidenced without stimulating the peripheral renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)
Foult
J M
JM
Chu Xavier Bichat, Paris, France.
Tavolaro
O
O
Antony
I
I
Nitenberg
A
A
D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D015773:Enalaprilat / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007261:Infusions, Intra-Arterial; D010101:Oxygen Consumption / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D015773:Enalaprilat