Impairment of vasodilator function in basilar arteries from aged rats.
OBJECTIVE
Aging is associated with a reduction in cerebral perfusion. Impaired vasodilatation in large brain arteries could be implicated. This study sought age-related changes in vasodilator responses to norepinephrine in rat basilar artery and investigated which aspects of norepinephrine's action are responsible. To study the effect of aging per se, we used the rat, an animal with resistance to development of age-related pathologies.


METHODS
Vascular responses were studied in basilar arteries from young (3 to 4 months old) and old (20 to 22 months old) normotensive Sprague-Dawley rats with wire myography. Endothelial structure was assessed with confocal microscopy.


RESULTS
There was no age-related difference in blood pressure and in KCl or 5-hydroxytryptamine (5-HT) contractions. Relaxation to bradykinin or its absence predicted an intact or denuded endothelium, confirmed by confocal microscopy. Norepinephrine produced concentration-dependent relaxation that was significantly smaller in old rats, with or without endothelium. This response was significantly smaller in endothelium-denuded vessels, or after preincubation with NG-nitro-L-arginine methyl ester or propranolol, but not with rauwolscine.


CONCLUSIONS
In old and young rats the vasodilator action of norepinephrine in basilar artery is dependent on beta-adrenoceptors and nitric oxide. The impaired vasodilatation to norepinephrine found in the basilar artery from old rats might be caused by (1) a reduction in nitric oxide production and/or release or (2) beta-adrenoceptor alteration at the endothelium and/or the vascular smooth muscle. This impairment of vasodilator function can be ascribed to the aging process per se and not to other age-related alterations, such as hypertension.
Arribas
S M
SM
Institute of Biomedical and Life Sciences, University of Glasgow, UK. S.Arribas@biomed.gla.ac.uk
Vila
E
E
McGrath
J C
JC
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000033:anatomy & histology / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D007545:Isoproterenol; D001920:Bradykinin; D009638:Norepinephrine