Effects of cholecalciferol on endothelial function and vascular tone in the porcine isolated coronary artery

R Hackney, B Cutts, M Randall. University of Nottingham, Nottingham, UK

The effects of both exogenous and endogenous vitamin D on cardiovascular regulation have recently received both epidemiological interest and interest on their impact on endothelial function. In the latter case there is evidence that cholecalciferol can restore endothelial function in rat models of hypertension [1,2]. The aim of this study was to determine the effects of cholecalciferol on endothelial function and whether it has direct vascular actions.

Porcine coronary arteries were obtained from peripubescent pigs and studied under myographic conditions in oxygenated (95% O2/ 5% CO2) Krebs’-Henseleit solution and placed under a resting tension of 7.84 mM. Following 2 challenges with 60 mM KCl, arteries were pre-contracted with the thromboxane mimetic, U46619. In some experiments, the effects of incubation of cholecalciferol (10μM) were assessed against endothelium-dependent relaxation to bradykinin under control conditions and in the combined presence of Nω -nitro-L-arginine methyl ester (L-NAME, 300μM) and indomethacin (10μM), to define the component mediated by endothelium-dependent hyperpolarization (EDH). In other experiments the time-dependent relaxant effects of cholecalciferol (10μM) were assessed against U46619-induced tone. In some of these experiments the role of protein synthesis was examined by the addition of cyclohexamide (10µM).

In arteries precontracted with U46619, bradykinin caused concentration-dependent vasorelaxation which was not affected by the presence of cholecalciferol. However, in the presence of L-NAME and indomethacin, cholecalciferol preserved the responses to bradykinin such that the maximum relaxation was 38.2±4.6% (mean+s.e.mean; n=11) in its presence compared to 22.9±5.4% (n =10) in control vessels (P<0.05; Student’s t-test). The presence of cholecalciferol also reduced contractile responses to U46619 and when it was added to U46619-precontracted tissues caused a time-dependent relaxation of tone, such that after 120 mins tone had decreased by 24.4+4.2% (n=8) compared to a 2.34+3.80% change in time controls (n=8; P<0.001). The time-dependent relaxation was unaffected by cyclohexamide (n=7).

In this study it was found that cholecalciferol had modest, protective effects on EDH-responses but more importantly was able to induce time-dependent relaxation of the coronary artery and so may influence vascular tone.

1. Borges et al., (1999). Br. J. Pharmacol., 127, 772–778.

2. Borges et al., (2002). Pathophysiology: the official journal of the International Society for Pathophysiology / ISP, 8(4), 263–268.