Author:
Williams Jeffrey G.,Rincon-Skinner Tibisay,Sun Dong,Wang Zipping,Zhang Suhua,Zhang Xiaoping,Hintze Thomas H.
Abstract
We examined the ability of cardiac endothelial nitric oxide synthase (eNOS) to couple myocardial oxygen consumption (MV̇o2) and oxygen delivery during pregnancy. Awake dogs were studied using echocardiography before and at 40 days, 50 days, and 60 days (60D) of pregnancy and at ∼14 days postpartum. Left ventricular eNOS, phosphorylated eNOS, and copper, zinc-superoxide dismutase (CuZnSOD or SOD-1) were determined by immunoblotting. MV̇o2 of left ventricular tissue samples was measured in vitro in response to increasing doses of bradykinin, enalapril maleate, and amlodipine. We examined the changes in passive diameter and flow-dependant arteriolar dilation of coronary arterioles. Echocardiography indicated increases in cardiac output (∼60%) during pregnancy. Myocardial eNOS (21 ± 4%), phosphorylated eNOS (19 ± 3%), and SOD-1 (61 ± 2.7%) protein levels were significantly increased at 60D. Bradykinin, enalapril maleate, and amlodipine (10−4 mol/l) decreased MV̇o2 in a nitric oxide-dependant manner (by 24 ± 1.3% in controls and 34 ± 2.2% at 60D; by 21 ± 1.1% in controls and 29 ± 1.1 at 60D; and by 22 ± 2.5% in controls and 26 ± 1.0% at 60D, respectively). Arterioles from pregnant dogs showed increased flow-dependant dilation in response to increased shear stress and larger passive diameter. Nitrite production was stimulated by bradykinin and carbachol in microvessels in vitro; pregnancy enhanced nitrite release. Myocardial eNOS, phosphorylated eNOS, and SOD-1 protein expression are increased during pregnancy, and this increase is associated with enhanced nitric oxide-dependant control of MV̇o2. Thus increases in eNOS and SOD-1 promote the coupling of oxygen delivery and efficiency in the heart during pregnancy.
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
24 articles.
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