Vascular contractile effect of urotensin II in young and aged rats: Influence of aging and contribution of endothelial nitric oxide

To elucidate whether aging influences the vascular contractile effect of urotensin II in rat thoracic aorta, and to evaluate the contribution of endothelial vasodilating substances in mediating the effect of urotensin II, the effect of urotensin II was examined in the vessels of young (2–3-month-old) and aged rat. Isolated rat aortic rings incubated in Krebs–Henseleit solution gassed with 95% O 2/5% CO 2 were stimulated with urotensin II, and the developed tension was measured. Urotensin II increased the developed tension, which was decreased by aging. In 2–3-months-old young aorta without endothelium, urotensin II (10 −10 to 10 −7) elicited a concentration-dependent aortic contraction to the maximal response almost equivalent to high KCl-induced contraction (79.4 ± 11.3% of KCl max). In the presence of endothelium, the urotensin II-induced vasoconstriction in young aorta was significantly attenuated to 33.3 ± 4.6% of KCl max. However, the contractile response was greater in the pretreatment with N G-nitro- l-arginine ( l-NNA) (100 μM) (50.3 ± 8.4% of KCl max in endothelial denuded aorta), suggesting the vasorelaxing role of endothelial nitric oxide. In 25–27-months-old aged rat aorta, the urotensin II-mediated contraction was remarkably decreased, both in the presence (6.3 ± 2.0% of KCl max) and absence (11.7 ± 3.0% of KCl max) of endothelium. A cyclooxygenase inhibitor, diclofenac (10 μM), did not have any effect on the urotensin II-induced contraction. These results suggest that urotensin II can induce vascular smooth muscle contraction in rat aorta, and there was an aging-related decline in the urotensin II-induced contraction. Endothelial production of nitric oxide in response to urotensin II but not cyclooxygenase metabolites such as prostacyclin may play a role in reducing the vascular constriction especially in young aorta.