Hyperplastic growth response of vascular smooth muscle cells following induction of acute hypertension in rats by aortic coarctation.
This study examines the growth response of vascular smooth muscle cells following induction of acute hypertension in rats by partial ligation of the abdominal aorta between the renal arteries. Systolic blood pressures proximal to the ligature increased dramatically within 3 days (from 135 +/- 3 to 195 +/- 7 torr) of surgery while pressures distal to the ligature were reduced from control values. The frequency of smooth muscle cells undergoing DNA replication was increased 25-fold in thoracic aortas of coarctation rats compared to sham-operated controls 9 days post-coarctation, while no differences were observed in cells in abdominal aortic segments 1 cm distal to the ligature. A small but significant increase in the frequency of tetraploid smooth muscle cells was observed in thoracic aortas of coarctation rats, but this increase accounted for less than 2% of the increase in medial DNA content. By far, the major growth response was hyperplasia, as evidenced by a 25% increase in thoracic aortic medial smooth muscle cell number without a change in mean cellular volume (micron3/cell) or mass (ng/cell). Whereas no evidence of endothelial denudation was observed in thoracic aortas of coarctation rats by scanning electron microscopy, endothelial cell turnover rates were increased 23-fold compared to controls, indicating that some form of endothelial "injury" or dysfunction was present. Consistent with this, morphological changes indicative of endothelial injury (e.g., subendothelial edema) were observed by light and transmission electron microscopy. The marked contrast between results of this study and our previous studies showing that aortic medial hypertrophy in spontaneously hypertensive and Goldblatt hypertensive rats was due to cellular hypertrophy and hyperploidy without hyperplasia, clearly demonstrates that the growth response of smooth muscle cells within a given blood vessel can be quite different, depending on the model of hypertension. It is suggested that a non-denuding form of endothelial "injury" may play an important role in the proliferative growth response of smooth muscle cells following induction of coarctation hypertension.
D000818:Animals; D001011:Aorta; D001794:Blood Pressure; D002452:Cell Count; D003250:Constriction; D004261:DNA Replication; D004727:Endothelium / Q000473:pathology / Q000648:ultrastructure; D006965:Hyperplasia; D006973:Hypertension / Q000209:etiology / Q000473:pathology*; D006984:Hypertrophy; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology* / Q000648:ultrastructure; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D011003:Ploidies; D051381:Rats; D011919:Rats, Inbred Strains