We have previously demonstrated that arterial diameter of isolated coronary arteries is governed by the relative, rather than the absolute, values of intravascular (IvP) and extravascular pressure (EvP). The elevation of EvP led to a reduction in arterial diameter. This was regained after IvP was increased to equal the transmural pressure (TmP) across the vessel walls prior to intervention (Azzawi & Austin, 2002). Here we examine the role of the endothelium in modulating vascular tone and in contributing to diameter regain achieved when IvP is increased.

Wistar rats were humanely killed by stunning followed by cervical dislocation and septal coronary arteries were dissected out. Each artery was mounted on a modified pressure myograph where they were constantly superfused with physiological salt solution (pH 7.4, 37 °C, 95 % air and 5 % CO₂). A lid was secured over the myograph chamber which allowed EvP to be altered (via a 95 % air and 5 % CO₂ source). The internal diameter of vessels was determined using a video dimension analyser. Data are given as means ± S.E.M.

At an IvP of 60 mmHg, and thus a net outward TmP of 60 mmHg, coronary arteries (mean internal diameter of 256 ± 10 µm, n = 8) developed myogenic tone (140 ± 10 µm). Elevation of EvP to 40 mmHg, which effectively reduced the net outward TmP to 20 mmHg, reduced the diameter of all vessels by 12 ± 2 %. Subsequent elevation of IvP to 100 mmHg, at a maintained EvP of 40 mmHg, to return net outward TmP to 60 mmHg increased arterial diameter to 105 ± 6 % of that observed at the original TmP of 60 mmHg (IvP of 60 mmHg and EvP of 0 mmHg). Endothelial denudation was then achieved by introduction of 4-5 air bubbles through the lumen. This abolished the endothelial-dependent dilator response to acetylecholine. Myogenic tone was increased in all vessels (mean increase in tone = 33 ± 12 µm). Elevation of EvP to 40 mmHg, reduced the diameter of all vessels by 24 ± 3 % (Student’s paired t test, P < 0.01). Subsequent elevation of IvP to 100 mmHg, increased arterial diameter to 89 ± 2 % (P < 0.01).

The effect of the nitric oxide synthase inhibitor N ^v{special}-nitro-L-arginine (L-NNA, 0.1 mmol l^-1) was then examined (mean internal diameter = 243 ± 11 µm, n = 10, tone = 120 ± 14 µm). Elevation of EvP to 40 mmHg reduced the diameter of all vessels by 11 ± 1 and 19 ± 4 % before and after inhibition, respectively (P < 0.05). Subsequent elevation of IvP to 100 mmHg, increased arterial diameter to 102 ± 1 and 89 ± 4 % before and after inhibition, respectively (P < 0.05). These results demonstrate that the endothelium may be an important modulator of arterial responsiveness to IvP-EvP intervention.

We gratefully acknowledge the support of the British Heart Foundation and The Royal Society.