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

Abstract

X, Hintze TH. Role of nitric oxide in the coupling of myocardial oxygen consumption and coronary vascular dynamics during pregnancy in the dog. Am J Physiol Heart Circ Physiol 293: H2479-H2486, 2007. First published July 20, 2007; doi:10.1152/ajpheart.00036.2006.-We examined the ability of cardiac endothelial nitric oxide synthase (eNOS) to couple myocardial oxygen consumption (MV O2) 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 ϳ14 days postpartum. Left ventricular eNOS, phosphorylated eNOS, and copper, zinc-superoxide dismutase (CuZnSOD or SOD-1) were determined by immunoblotting. MV O2 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 (ϳ60%) during pregnancy. Myocardial eNOS (21 Ϯ 4%), phosphorylated eNOS (19 Ϯ 3%), and SOD-1 (61 Ϯ 2.7%) protein levels were significantly increased at 60D. Bradykinin, enalapril maleate, and amlodipine (10 Ϫ4 mol/l) decreased MV O2 in a nitric oxide-dependant manner (by 24 Ϯ 1.3% in controls and 34 Ϯ 2.2% at 60D; by 21 Ϯ 1.1% in controls and 29 Ϯ 1.1 at 60D; and by 22 Ϯ 2.5% in controls and 26 Ϯ 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 oxidedependant control of MV O2. Thus increases in eNOS and SOD-1 promote the coupling of oxygen delivery and efficiency in the heart during pregnancy. gene expression PREGNANCY IN HUMANS IS ASSOCIATED with an early rise in plasma volume, which is increased further in the second trimester and then increases only slightly further until delivery. The average increase in plasma volume is 40% over normal values (12). Along with this volume overload state, there is an increase in cardiac output (20). In humans, cardiac output increases an average of 40% (from 5 to 7 l/min) in women at rest in the supine position. The increase in output is detectable starting at week 5 and then levels off at around week 20. A portion of the increase in cardiac output is attributable to an increase in stroke volume (3,6). By midpregnancy, the stroke volume has increased upward of 30%. The increase in cardiac output is at least partially achieved by an enhanced myocardial performance (9) and a relative tachycardia. The basal heart rates of women rise significantly by the 4th wk of pregnancy and reach a peak at the 36th wk (4).The increase in cardiac output is associated with a decrease in total peripheral resistance (23), ...

Hemodynamic gestational adaptation in bitches

“…However, the reduction in PVR mentioned previously also contributed to this effect (SPOTSWOOD et al, 2006). As a result of the volume overload and increased demands on the myocardium, which starts with an elongation of the muscle fibers to accommodate the rising blood flow, the left ventricle develops eccentric hypertrophy, a physiological fact that has been observed in women, female dogs and mice (EGHBALI et al, 2005;WILLIAMS et al, 2007;ABOTT, 2010;.…”

“…Two-dimensional, M-mode, color and tissue Doppler echocardiography are all used in pregnant women to assess systolic and diastolic function (VALENSISE et al, 2000;FOK et al, 2006), demonstrating the changes in the shape of the left ventricle that occur during pregnancy to adapt to the vascular load resulting from the gestational process (VALENSISE et al, 2000;DESAI et al, 2004). Few studies have looked at these changes in dogs, and these have related to the reduction in afterload, the increase in systolic function and cardiac hypertrophy during the course of pregnancy (WILLIAMS et al, 2007;BLANCO et al, 2011;.…”

“…In women, the majority of these changes can be observed from the first trimester of pregnancy (DUVEKOT et al, 1993), while in dogs it is thought that from the thirtieth day of gestation there is an elevation in the shortening fraction (WILLIAMS et al, 2007;BLANCO et al 2011) that may result from the improvement in systolic function and consequent increased cardiac output , principally due to the greater plasma volume (KITTLESON, 1998). Shortening fraction is directly proportional to the end-systolic dimensions of the left ventricular chamber, which are greater during the period prior to delivery, and reduce gradually as the plasma volume normalizes (ABBOTT, 2010).…”

“…Shortening fraction is directly proportional to the end-systolic dimensions of the left ventricular chamber, which are greater during the period prior to delivery, and reduce gradually as the plasma volume normalizes (ABBOTT, 2010). By the fortieth day, there is an effective increase in systolic volume and output (WILLIAMS et al, 2007) that occurs due to the reduction in total vascular resistance that accompanies the formation of the uteroplacental vascular system and contributes to increased blood supply to the conceptus (SPOTSWOOD et al, 2006;WILLIAMS et al, 2007). During this period, vascular compliance increases to accommodate the greater volume of blood (VALENSISE et al, 2000;BLANCO et al, 2009).…”

“…After 50 to 60 days, increases can be observed in end-systolic and end-diastolic left ventricular diameter (LVDs and LVDd), left ventricular free wall dimensions (LVFW) and systolic volume, with heart rate and cardiac output also reaching higher values (WILLIAMS et al, 2007;BLANCO et al, 2011). These structural changes are caused mainly by the volume overload that drives the physiological adaptation of the fibers of the myocardium, evident in the increased internal diameter of the left ventricular chamber and the free wall in systole without increased thickness in diastole, demonstrating hypertrophy to be stable (EGHBALI et al, 2005;WILLIAMS et al, 2007;ABBOT, 2010).…”