AGE-RELATED-CHANGES IN THORACIC AORTA OF OBESE ZUCKER RATS

Studies were performed on the ontogeny of arterial blood pressure and functional properties of the thoracic aorta in lean (L) and obese (O) male Zucker rats at ages of 6-36 wk. Body weight was larger in the O than the L at all ages, with differences reaching values of 200-250 g at ages over 24 wk (at 33-36 wk: L = 510 +/- 9 and O = 730 +/- 15 g). Systolic blood pressure was lower in young O compared with L (6-15 wk) but increased with age at a rate seven times greater in O than in L. For ages of 33-36 wk, systolic pressure was significantly higher in O compared with L (O = 132 +/- 2 vs. L = 122 +/- 2 mmHg). Total serum cholesterol (at 36 wk: L = 278 +/- 31 and O = 354 +/- 12 mg/dl) and triglycerides (at 36 wk: L = 493 +/- 71 and O = 1,618 +/- 220 mg/dl), as well as glucose levels, increased with age in both groups and were significantly higher in O at all ages. Serum levels of thyroxine but not triiodothyronine were significantly lower in O at all ages. No differences were found in passive mechanics at any age. Values of maximum active stress with smooth muscle activation by 75 mM K+ plus 10-mu-M norepinephrine were significantly higher at 24 and 36 wk in O (at 36 wk: L = 573 +/- 42 and O = 821 +/- 89 x 10(3) dyn/m2). No significant differences were found in concentration-response relations of thoracic aorta to KCl concentrations or in acetylcholine- (except at 12 wk), nitroprusside-, isoproterenol-, or forskolin-mediated relaxations. Aorta from O had higher sensitivity to norepinephrine at 12 and 24 wk and to serotonin at 12, 24, and 36 wk. These differences in sensitivity persisted in aorta following endothelium removal. A more rapid increase of arterial pressure occurs in O, which is associated at 24-36 wk with larger maximum active stress as well as with more sensitive contractile responses to norepinephrine at 12 and 24 wk and to serotonin for 12-36 wk. A role for these changes in smooth muscle function in the greater age-related changes in arterial pressure in obese Zucker rats is suggested.