Acute pressure overload reduced veratrine-induced increase in coronary blood flow by 66% (from 23 to 7 mL/min), causing endothelial stunning via oxidant processes involving angiotensin II.
Coronary microvascular endothelial stunning following acute pressure overload is mediated by oxidant stress involving angiotensin II-induced NAD(P)H oxidase activation.
Effect estimate: reduced by 66%
Absolute Event Rate: 7% vs 23%
BACKGROUND: Few studies have examined the effect of acute pressure overload on endothelial function in the coronary microcirculation. METHODS AND RESULTS: In instrumented conscious dogs with heart rate held constant, veratrine caused a cholinergic nitric oxide (NO)-dependent increase in coronary blood flow by 23+/-3 mL/min (Bezold-Jarisch reflex). Ten minutes after release of constriction of the ascending aorta to increase left ventricular (LV) systolic pressure to 214+/-5 mm Hg for 30 minutes, the veratrine-induced increase in coronary blood flow (7+/-1 mL/min) was reduced by 66% and remained depressed for 2 hours (ie, endothelial stunning ES). Nitrite production from isolated coronary microvessels during ES was not different from normal. Ascorbic acid (AA), losartan, or apocynin prevented ES. Myocardial oxygen consumption (MVO2) of LV tissue was measured in vitro in response to bradykinin with preincubation of angiotensin II for 30 minutes. Bradykinin (10(-4) mol/L)-induced reduction in MVO2 was reversed in a concentration-dependent manner by angiotensin II (38+/-1% versus 19+/-2% at 10(-8) mol/L) and restored by coincubation of AA (37+/-2%), tempol (33+/-2%), losartan (34+/-2%), or apocynin (36+/-1%). Exogenous NO-induced reduction in MVO2 was not altered by angiotensin II. Angiotensin II increased lucigenin-detectable superoxide anion in LV tissue in a manner that was inhibited by bradykinin, AA, tempol, losartan, or apocynin. CONCLUSIONS: Endothelial stunning is caused by oxidant processes inhibited by ascorbate, and the activation of NAD(P)H oxidase by increased angiotensin II plays an important role in this process.
Kinugawa et al. (Tue,) conducted a other in Coronary microvascular endothelial stunning. Acute pressure overload vs. Baseline was evaluated on Veratrine-induced increase in coronary blood flow (reduced by 66%). Acute pressure overload reduced veratrine-induced increase in coronary blood flow by 66% (from 23 to 7 mL/min), causing endothelial stunning via oxidant processes involving angiotensin II.
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