Hirudin (Desulfated, 54-65) causes contracton of canine coronary arteries which is attenuated by calcium-channel blockers

Background: Hirudin is a novel antithrombin agent with potent anticoagulatory properties. Previous studies have demonstrated that hirudin stimulates the release of nitric oxide in porcine pulmonary arteries. We investigated hirudin for its direct effects on coronary arteries. Methods and Results: Canine coronary arteries were mounted in organ chambers and precontracted with prostaglandin F₂ α(2x10^-6M). In arteries with intact endothelium, hirudin (10^-1 to 10^-6M) increased vascular tension 33.6±9.0% above baseline tension (n=10, p<0.05 ANOVA). In arteries denuded of endothelium, hirudin increased vascular tension 31.8±11.2% above baseline tension (n=8, p<0.05),demonstrating that the hirudin-mediated contractions were endothelium independent. Pretreatment of the coronary arteries with either verapamil (10^-4M) or nifedipine (10^-4M) for one hour attenuated hirudin-mediated vascular contractions. Whereas control arteries contracted 26.4±10.3% above baseline tension, hirudin administration increased vascular tension 3.8±7.0% above baseline tension in arteries pretreated with verapamil (n=6, p<0.05 vs. control) and 6.2±12.4% above baseline tension in arteries pretreated with nifedipine(n=6,p<0.05). Conclusions: The present study demonstrates that hirudin induces endothelium-independent contractions of canine coronary arteries. Attenuation of these contractions by calcium-channel blockers suggests a possible mechanism by which hirudin mediates coronary artery constriction.