+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Angiotensin-converting enzyme inhibition preserves endothelium-dependent coronary microvascular responses during short-term ischemia -reperfusion



Angiotensin-converting enzyme inhibition preserves endothelium-dependent coronary microvascular responses during short-term ischemia -reperfusion



Circulation 93(3): 544-551



Background: Chronic angiotensin-converting enzyme (ACE) inhibition initiated days to weeks after acute myocardial infarction can reduce ventricular dilatation and improve patient survival. However, the effects on coronary vascular and myocardial function of very early ACE inhibitor therapy for acute myocardial infarction remain unresolved. Methods and Results: Hemodynamics, segmental shortening, coronary blood flow, and in vitro coronary microvascular relaxation responses were studied in noninstrumented control pigs (n=8) and pigs subjected to 30 minutes of left anterior descending ischemia followed by administration of 30 mL IV normal saline (IR-saline, n=8), 5 mg(kg IV captopril (IR-captopril, n=6), or 1.5 mg/kg IV enalaprilat (IR-enalaprilat, n=6) before 1 hour of reperfusion. Hemodynamics were similar at baseline, end of ischemia, and end of reperfusion. However, coronary blood flow immediately on reperfusion was significantly enhanced in the IR-enalaprilat cohort (59+-10 mL/min) compared with the IR-saline group (32+-3 mL/min, P lt .05). Segmental shortening in the dyskinetic ischemic region improved only minimally at the end of reperfusion to 1+-2%, -7+-3%, and -2+-6% for the IR-saline, IR-captopril, and IR-enalaprilat groups, respectively (P lt .05, IR-captopril versus IR-saline). Arteriolar microvascular endothelium-dependent responses to ADP (P lt .01) and calcium ionophore A23187 (P lt .01) were impaired after ischemia-reperfusion, whereas bradykinin responses were preserved (P=.95). Endothelium-dependent venular responses to ADP and serotonin were maintained despite ischemia-reperfusion. Endothelium-independent responses to sodium nitroprusside were unaltered in arterioles and venules. Either captopril or enalaprilat restored ADP and A23187 arteriolar responses to control levels and increased bradykinin responses above control levels. Conclusions: Brief ischemia followed by reperfusion induces arteriolar microvascular endothelial dysfunction, while venular endothelial function is preserved in this porcine model. ACE inhibition enhances coronary blood flow at the time of reperfusion and can prevent impairment of endothelium-dependent arteriolar responses. However, ACE inhibition does not enhance ventricular segmental shortening acutely despite improved microvascular endothelial function and augmented postischemic coronary blood flow in this model of ischemia-reperfusion.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 008163283

Download citation: RISBibTeXText

PMID: 8565174


Related references

Effect of angiotensin converting enzyme inhibition on endothelium dependent responses in isolated coronary arteries. European Heart Journal 10(ABSTR Suppl.): 5, 1989

Endothelium-dependent responses and inhibition of angiotensin-converting enzyme. Clinical & Experimental Pharmacology & Physiology. 23(8): S23-S29, 1996

In women with symptoms of cardiac ischemia, nonobstructive coronary arteries, and microvascular dysfunction, angiotensin-converting enzyme inhibition is associated with improved microvascular function A double-blind randomized study from the National Hea. 2011

In women with symptoms of cardiac ischemia, nonobstructive coronary arteries, and microvascular dysfunction, angiotensin-converting enzyme inhibition is associated with improved microvascular function: A double-blind randomized study from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE). American Heart Journal 162(4): 678-684, 2011

Inhibition of angiotensin converting enzyme augments the endothelium dependent relaxation to bradykinin in human coronary artery. European Heart Journal 11(ABSTR Suppl.): 151, 1990

Angiotensin-converting enzyme inhibition in patients with coronary artery disease and preserved left ventricular function Ischemia Management with Accupril post-bypass graft via inhibition of angiotensin-converting enzyme (IMAGINE) compared with the other major trials in coronary artery disease. American Heart Journal 151(6): 1240-1246, 2006

Angiotensin-converting enzyme inhibition prevents coronary microvascular remodeling in rats induced by long-term blockade of nitric oxide synthesis. Circulation 92(8 Suppl. ): I697, 1995

Normoxic lung ischemia/reperfusion accelerates shedding of angiotensin converting enzyme from the pulmonary endothelium. American Journal of Respiratory and Critical Care Medicine 156(4 Pt 1): 1114-1119, 1997

Angiotensin-converting enzyme inhibition with intracoronary enalaprilat augments metabolic coronary vasodilation via endothelium-dependent mechanism in the human failing heart. European Heart Journal 16(ABSTR Suppl. ): 455, 1995

Renal haemodynamics during short-term angiotensin converting enzyme inhibition in normotensive normoalbuminuric insulin dependent diabetics. Diabetes Research 11(1): 9, 1989

Angiotensin-(1-7) augments endothelium-dependent relaxations of porcine coronary arteries to bradykinin by inhibiting angiotensin-converting enzyme 1. Journal of Cardiovascular Pharmacology 63(5): 453-460, 2014

Long-term angiotensin-converting enzyme inhibition reduces plasma asymmetric dimethylarginine and improves endothelial nitric oxide bioavailability and coronary microvascular function in patients with syndrome X. American Journal of Cardiology 90(9): 974-982, 2002

Potentiation of endothelium-dependent relaxations to bradykinin by angiotensin I converting enzyme inhibitors in canine coronary artery involves both endothelium-derived relaxing and hyperpolarizing factors. Circulation Research 71(1): 137-144, 1992

Left ventricular hypertrophy and coronary microvascular endothelium in the guinea-pig Phenotypic changes in nitric oxide synthase and angiotensin converting enzyme activity. British Journal of Pharmacology 120(PROC Suppl. ): 99P, 1997