Effects of aging on responses of cerebral arterioles

Our goal was to determine whether responses of cerebral arterioles are altered in aged rats. We examined responses of cerebral arterioles in adult (6-8 mo old) and aged (22-24) mo old) Wistar rats to superfusion of acetylcholine and bradykinin, which presumably produce dilatation by releasing an endothelium-derived relaxing factor (EDRF), and to nitroglycerin, which produces dilatation by a direct effect on vascular muscle. In adult rats, cerebral arterioles dilated by 11 +/- 2% (SE) to acetylcholine (10(-5) M) and by 21 +/- 3% to bradykinin (10(-7) M). In contrast, arterioles in aged rats dilated by only 3 +/- 1% to acetylcholine and by 7 +/- 3% to bradykinin. Vasodilatation in response to nitroglycerin was similar to adult and aged rats. We also examined responses of cerebral arterioles to products released by platelets (ADP, serotonin, and thromboxane). ADP (10(-4) M) increased pial arteriolar diameter by 26 +/- 5% in adults rats and only 12 +/- 3% in aged rats. Serotonin (10(-5) M) produced modest vasodilatation in adult rats (7 +/- 1%) but modest vasoconstriction in aged rats (-5 +/- 2%). Vasoconstriction in response to a thromboxane A2 analogue (U 46619) was similar in adult and aged rats. Indomethacin (10 mg/kg iv) did not affect responses to acetylcholine, serotonin, and ADP in aged rats. Thus dilator responses of cerebral arterioles to agonists that may release EDRF are altered in aged compared with adult rats. Impaired vasodilatation in aged rats does not appear to be related to production of a cyclooxygenase constrictor substance.