The effects of coarctation hypertension upon vascular inositol phospholipid hydrolysis in Wistar rats.

In order to examine the effects of imposing an acute pressure load upon vascular structure and phosphoinositide hydrolysis, aortic medial thickness, cross-sectional area, cell nuclear counts and inositol phosphate accumulation were measured in Wistar rats with experimental coarctation and sham-operated controls at 3, 9 and 20 days after surgery. Compared to sham-operated animals, rats with coarctation had significantly higher carotid artery pressures throughout the study. Below the ligature, femoral arterial pressure was significantly lower in animals with coarctation. Proximal to the coarctation, there was an increase in aortic medial cross-sectional area and medial thickness but no increase in nuclear counts, suggesting the induction of hypertrophy; statistically significant changes were present at 9 and 20 days. Distal to the ligature only small structural changes were observed indicating some atrophy had occurred. Inositol phosphate accumulation had increased slightly at 3 days in proximal aortae from ligatured rats, and was significantly raised at 9 and 20 days; no such changes were recorded below the coarctation. These data indicate that the increased load upon the proximal aorta initiates increased inositol phosphate production through local mechanisms. Whilst a causal link has not been conclusively established between phosphoinositide turnover and hypertrophy, the association between the two in these studies is consistent with the hypothesis that the induction of increased cell phosphoinositide metabolism contributes, at least in part, to the proximal aortic structural changes observed in this model.