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Role of nitric oxide in the coupling of myocardial oxygen consumption and coronary vascular dynamics during pregnancy in the dog

New York Medical College, Valhalla, New York

Submitted 7 January 2006 ; accepted in final form 16 July 2007

We examined the ability of cardiac endothelial nitric oxide synthase (eNOS) to couple myocardial oxygen consumption (MO₂) 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. MO₂ 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 MO₂ 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 MO₂. Thus increases in eNOS and SOD-1 promote the coupling of oxygen delivery and efficiency in the heart during pregnancy.

gene expression

This article has been cited by other articles:

				J. G. Williams, C. Ojaimi, K. Qanud, S. Zhang, X. Xu, F. A. Recchia, and T. H. Hintze Coronary nitric oxide production controls cardiac substrate metabolism during pregnancy in the dog Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2516 - H2523. [Abstract] [Full Text] [PDF]