We have previously demonstrated that changes in both intravascular pressure (IvP) and extravascular pressure (EvP) will modify arterial diameter (Azzawi & Austin, 2002) of isolated rat coronary arteries. Here, we specifically examine, using novel methodology, whether isolated rat coronary arteries can actively regulate their diameter during more sustained elevations of EvP.

Male Wistar rats were humanely killed by stunning and cervical dislocation. Septal coronary arteries were dissected out and mounted on a modified pressure myograph, superfused with physiological salt solution (PSS, pH 7.4, 37 °C, 95 % air-5 % CO₂). A secure lid over the myograph chamber allowed EvP to be elevated (via a 95 % air-5 % CO₂ source) over sustained periods. The internal vessel diameter was determined using a video dimension analyser. EvP was elevated in 20 mmHg increments over the range 20-100 mmHg, and stable diameter measurements recorded. Evidence of active diameter regulation was also noted at each step. To determine the passive characteristics of arteries this was repeated in Ca²⁺-free PSS. In some arteries, endothelium denudation was achieved by introduction of four to five air bubbles through the lumen. This abolished the endothelial-dependant dilator response to acetylcholine (10 µM). Data given as means ± S.E.M.

Coronary arteries had a mean diameter of 229 ± 16 µm (n = 6) when pressurised to an IvP of 60 mmHg (at zero elevated EvP, i.e. atmospheric pressure). All arteries developed myogenic tone (mean active diameter = 142 ± 15 µm, tone = 99 ± 12 µm). Elevation of EvP produced an immediate decrease in diameter in all arteries. Evidence of active regulation was observed in all arteries, such that maintained active diameter values were essentially unchanged over an EvP range of 20-60 mmHg (138 ± 15 µm at 20 mmHg; 136 ± 16 µm at 40 mmHg; 136 ± 15 µm at 60 mmHg). Stable diameters were achieved within 1-9 min. Active diameters were significantly lower than passive diameters at 20, 40, 60 (Student’s paired t test, P < 0.01) and 100 mmHg (P < 0.05) EvP. The effect of endothelial denudation on the autoregulatory response was then examined (mean diameter 249 ± 13 µm, n = 5). Myogenic tone was increased in all vessels (mean increase in tone = 43 ± 16µm). The active regulation of diameter at an EvP of 40 mmHg achieved in endothelium-intact vessels was lost subsequent to denudation.

Thus we demonstrate that coronary vessels show active regulation of coronary artery diameter in response to a sustained elevation of EvP. In addition, we show that such regulation is modulated by endothelium-derived mediators.

We gratefully acknowledge the support of the British Heart Foundation.