Reduced systolic pressure load decreases cell-cycle activity in the fetal sheep heart.
The fetal heart is highly sensitive to changes in mechanical load. We have previously demonstrated that increased cardiac load can stimulate cell cycle activity and maturation of immature cardiomyocytes, but the effects of reduced load are not known. Sixteen fetal sheep were given either continuous intravenous infusion of lactated Ringer solution (LR) or enalaprilat, an angiotensin-converting enzyme inhibitor beginning at 127 days gestational age. After 8 days, fetal arterial pressure in the enalaprilat-infused fetuses (23.8 +/- 2.8 mmHg) was lower than that of control fetuses (47.5 +/- 4.7 mmHg) (P < 0.0001). Although the body weights of the two groups of fetuses were similar, the heart weight-to-body weight ratios of the enalaprilat-infused fetuses were less than those of the LR-infused fetuses (5.6 +/- 0.5 g/kg vs. 7.0 +/- 0.6 g/kg, P < 0.0001). Dimensions of ventricular myocytes were not different between control and enalaprilat-infused fetuses. However, there was a significant decrease in cell cycle activity in both the right ventricle (P < 0.005) and the left ventricle (P < 0.002) of the enalaprilat-infused fetuses. Thus, we conclude a sustained reduction in systolic pressure load decreases hyperplastic growth in the fetal heart.
O'Tierney
P F
PF
Heart Research Center, Oregon Health and Sciences Univ., Portland, OR 97239, USA.
Anderson
D F
DF
Faber
J J
JJ
Louey
S
S
Thornburg
K L
KL
Giraud
G D
GD
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D048429:Cell Size; D015773:Enalaprilat / Q000008:administration & dosage; D005318:Fetal Heart / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D020567:Fetal Weight; D005865:Gestational Age; D006965:Hyperplasia; D007262:Infusions, Intravenous; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology*; D010100:Oxygen / Q000097:blood; D012756:Sheep; D013599:Systole; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002245:Carbon Dioxide; D015773:Enalaprilat; D010100:Oxygen