Age-related changes in carotid vascular responses to noradrenaline and nitric oxide synthase inhibitor

ABSTRACT

The aim of the present work was to study whether age alters the constrictor responses evoked by the sympathetic transmitter Noradrenaline in the carotid circulation in the rat. Another aim was to test whether age changes the influence of tonically synthetised nitric oxide [NO] on arterial blood pressure [ABP] and on carotid circulation. Further, to investigate the effect of NO synthesis inhibition on carotid vascular responses euoted by noradrenaline in three age groups of rats. In anaesthetised rats aged 4-5, 10-12 and 42-44 weeks [young, mature, middle-aged respectively], carotid blood flow [CBF] and carotid vascular conductance [CVC] were recorded during infusion of noradrenaline [2.5/micro g.kg[-1]], before and after a bolus dose of the nitric oxide synthase inhibitor L-NAME [10mg.kg[-1]]. In mature and middle-aged rats, noradrenaline infusion increased mean ABP to 180mmHg, but only to 150mmHg in young rats. Concomitantly, CVC decreased more in mature and middle-aged, than in young rats CBF remained constant in young, but decreased in mature and middle-aged rats. NO synthase inhibition produced similar increases in baseline ABP in all groups, but decreased CVC and CBF more in mature and middle-aged rats. Following NO inhibition, noradrenaline infusion increased ABP to similar levels as before in young and mature rats, but to higher levels in middle-aged rats. Further, CVC fell in young and mature, but not in middle-aged rats, in whom CBF increased with ABP.Thus, in young rats there was a weak noradrenaline-evoked pressor response and decrease in CVC. By contrast, in mature and middle-aged rats, noradrenaline evoked a strong pressor response and decrease in CVC. In young and mature rats, NO seems not to limit the noradrenaline-evoked increases in ABP or decreases in CVC. However, by middle age NO limits noradrenaline-evoked pressor response and prevents breakthrough of CBF Autoregulation. The three age groups showed good autoregulatory response of carotid circulation during a pressor response induced by noradrenaline. However, the constrictor responses evoked by noradrenaline is weak in youngs before the age of sexual maturity. On the other hand, by middle-age and well before old age, the constrictor influences of noradrenaline in carotid circulation have begun to weaken. Moreover, by middle age, the dilator influence of NO helps to prevent breakthrough of Autoregulation of CBF at the upper end of the range