Adenosine is a local regulator of physiological functions which has been shown to be a vasodilator (Olsson & Pearson, 1990). We have previously shown that adenosine produces a dilatation of pressurised rat coronary resistance arteries with myogenic tone (Lynch et al. 2002). The current study examines the role of the endothelium-derived nitric oxide (NO) in mediating the adenosine-induced dilatation of pressurised rat coronary arteries with myogenic tone. Also the role of KATP channels in adenosine-induced dilatation was investigated during NO inhibition.
Wistar rats were killed by cervical dislocation and septal coronary arteries were dissected. Arteries were pressurised to 60 mmHg and checked for leaks. The inner diameter and wall thickness was continually monitored using a video dimension analyzer. Once myogenic tone had stabilised the presence of a functional endothelium (FE) was assessed by a dilatory response to acetylcholine (10-5 M) of greater than 20 % (n = 5). Vessels displaying a response of less than 20 % were deemed to be have impaired endothelial (IE) function (n = 7). After control responses, the dilatation to adenosine (10-4 M) was assessed in the presence of the NO synthase inhibitor L-NAME (10-5 M), followed by L-NAME and glibenclamide (5 X 10-6 M).
The mean ± S.E.M. diameter of vessels used was 221.0 ± 13.1 µm. The mean dilatation of vessels to acetylcholine was 27.2 ± 1.9 % in the FE group and 7.7 ± 1.8 % in the IE group. The mean ± S.E.M. increase in diameter of FE vessels in response to adenosine was 42.6 ± 9.7 µm. This dilatation was significantly reduced following incubation with L-NAME to 22.1 ± 7.3 µm (P < 0.05, Student’s paired t test). The mean increases in diameter of IE vessels in response to adenosine was 23.3 ± 3.7 µm. This dilatation was not significantly reduced following incubation with L-NAME (17.7 ± 5.5 µm (P = 0.5, paired t test). The adenosine-induced dilatation of IE vessels was significantly reduced compared with FE vessels (P < 0.05, unpaired t test). Addition of glibenclamide in the presence of L-NAME did not alter the adenosine-induced dilatation in either the FE or IE group.
The current study demonstrates that the adenosine-induced dilatation of pressurised rat coronary arteries with myogenic tone is partially dependent on endothelium-derived NO, the remaining dilatation is endothelium independent and insensitive to glibenclamide.
This work was funded by The British Heart Foundation.