Age-related changes in carotid vascular responses to adenosine and nitric oxide in the rat: in vitro and in vivo studies.
We investigated how the ability of adenosine to release nitric oxide (NO) from carotid artery in vitro, and dilator responses evoked in carotid circulation in vivo by systemic infusion of adenosine, change with age in rats of 4-5, 10-12, and 42-44 wk (juvenile, mature, and middle aged). A secondary aim was to follow age-related changes in carotid/cerebral autoregulation. In opened carotid artery, graded doses of adenosine evoked graded increases in NO output measured with a NO sensor that were greater in mature and middle-aged than juvenile rats. Infusion of adenosine to reduce mean arterial pressure (ABP) to approximately 60 mmHg increased carotid vascular conductance (CVC) in all groups, but the increase was larger in mature rats; carotid blood flow (CBF) was unchanged in juvenile, increased in mature, but fell in 4/8 middle-aged rats. The NO synthase inhibitor nitro l-arginine methyl ester (l-NAME; 10 mg/kg iv) increased baseline ABP in all groups but caused larger percentage reductions in baseline CVC and CBF in mature and middle-aged than juvenile rats. Thereafter, the adenosine-evoked increase in CVC was unchanged in juvenile and middle-aged rats, yet CBF remained constant in juvenile but increased in middle-aged rats. In mature rats, the evoked increases in CVC and CBF were attenuated and further attenuated by l-NAME at 30 mg/kg. We propose that the ability of adenosine to release NO and cause vasodilation in the carotid artery and its circulation is greater in mature, than juvenile or middle-aged rats, but NO has greater tonic dilator influence in carotid circulation of mature and middle-aged than juvenile rats. By middle age, the lower limit of cerebral autoregulation has increased such that the tonic dilator influence of NO on ABP and CVC limits autoregulation of CBF to depressor responses. However, partial NO synthase inhibition overcomes this impairment, raising baseline ABP and allowing adenosine-evoked increases in CVC to increase CBF.
Omar
Nisreen Mansour
NM
School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, The Medical School, Birmingham B15 2TT, United Kingdom.
Marshall
Janice M
JM
D000241:Adenosine / Q000008:administration & dosage*; D000367:Age Factors; D000375:Aging; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006706:Homeostasis; D007262:Infusions, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester