Proceedings of The Physiological Society

University of Cambridge (2004) J Physiol 555P, PC16


Dilator responsiveness to adenosine and the role of nitric oxide (NO) in the carotid circulation of young and mature rats under anaesthesia

Nisreen M. Omar and Janice M. Marshall

Department of Physiology, The Medical School, Birmingham B15 2TT, UK

We recently reported (Omar & Marshall, 2002) that the density of sympathetic innervation of middle cerebral and basilar arteries is substantially greater in mature than young Wistar rats. In the present study on young and mature male Wistar rats (~5, 12 weeks old respectively), we tested whether maturation affects vasodilator responses to adenosine.

In Study 1, carotid arteries (CA) were removed from rats under anaesthesia (3 % halothane in 3 l min-1 O2). NO released from endothelial surface of the opened CA was measured directly using an NO sensitive electrode. In CAs from 6 young rats, any increase in NO output evoked by graded concentrations of adenosine (1 X 10-4-5 X 10-3 M) was not dose-related (from 8.064 ± 2.814 to 8.847 ± 2.472 nM NO, mean ± S.E.M. with 1 X 10-4 and 5 X 10-3 M adenosine respectively). By contrast, in CAs from 7 mature rats, NO release evoked by adenosine was dose-related, ranging from 5.823 ± 1.153 to 16.126 ± 3.345*** nM NO (***; P < 0.001, ANOVA repeated measures) as described by Ray et al, (2002) for rat thoracic aorta.

In Study 2, on rats anaesthetised with Saffan (7-12 mg. kg-1. h-1), carotid blood flow (CBF) and carotid vascular conductance (CVC) were recorded during infusion of adenosine (2.4-2.8 mg kg-1 min-1 iv, for 3 min) to reduce arterial blood pressure (ABP) to ~60 mm Hg. In 7 young rats, adenosine evoked an increase in CVC (from 0.013 ± 0.001 to 0.033 ± 0.006††ml min-1 mmHg-1; ††, †: P < 0.01, 0.05, Student's paired t test), but no change in CBF. By contrast, in 7 mature rats, a similar fall in ABP was accompanied by greater increase in CVC (from 0.019 ± 0.009 to 0.062 ± 0.003††ml min-1 mmHg-1) and also by an increase in CBF (from 2.32 ± 0.44 to 3.71 ± 0.56††ml min-1). In young rats, the NO synthesis inhibitor L-NAME (10 mg kg-1) decreased baseline CVC to (0.009 ± 0.001†† ml min-1 mmHg-1), but had no effect on the adenosine-evoked responses. However, in mature rats, L-NAME decreased baseline CVC to 0.007 ± 0.001†† ml min-1 mmHg-1 and reduced the increase in both CVC and CBF induced by adenosine to 0.032 ± 0.006†† ml min-1 mmHg-1 and 2.095 ± 0.39† ml min-1 respectively. At the end of experiments all animals were humanely killed.

These results suggest that the carotid circulation of young rats has a decreased dilator responsiveness to adenosine compared to mature rats and that may be explained, at least in part, by a lower NO output in response to adenosine in young rats.

Where applicable, experiments conform with Society ethical requirements