Objective: To evaluate the role of potassium channels in the regulation of coronary hemodynamics in experimental hypercholesterolemia. Background: Potassium (K +) channels play an important role in coronary vasoregulation. It has previously been demonstrated that experimental hypercholesterolemia is associated with altered coronary vasomotion; however, the role of K + channels in modulating coronary blood flow in this pathophysiologic state has not been evaluated. Methods and results: Pinacidil (group 1, n = 5) at 2 μg/kg per min, glibenclamide (group 2, n = 5), or N-monomethyl-L-arginine (LNMMA) (group 3, n = 4) at 50 μg/kg per min were infused into the left anterior descending artery of pigs prior to and following 10 weeks of 2% cholesterol diet. After 10 weeks of cholesterol feeding, intracoronary pinacidil resulted in a significant increase in coronary blood flow (CBF) and coronary artery diameter (CAD) compared to the normolipidemic state (111 ± 10 versus 59 ± 12%, and 6 ± 1.1 versus 2.7 ± 1.0%, respectively, P < 0.05 for both comparisons), whereas intracoronary glibenclamide resulted in a significant decrease in CBF and CAD compared to the normolipidemic state (-17 ± 5 versus 5 ± 6%, and -0.8 ± 1.4 versus 3.6 ± 1.6%, respectively, P < 0.05 for both comparisons). The effect of intracoronary LNMMA on CBF and CAD was significantly attenuated after 10 weeks of cholesterol feeding as compared to the normolipidemic state (-47 ± 5.4 versus -0.8 ± 6.8%, and -19.4 ± 5.7 versus -2.3 ± 3.3%, respectively, P < 0.05 for both comparisons). Furthermore, pretreatment with intracoronary LNMMA did not alter the CBF response to pinacidil in normal pigs (group 4, n = 4) (57.4 ± 19 versus 59 ± 12%, P = NS). Conclusions: The current study demonstrates an enhanced effect of coronary K + channel modulation and confirms the attenuated basal NO activity previously reported in experimental hypercholesterolemia. Acute withdrawal of basal NO activity alone, however, does not explain the enhanced effect of coronary K + channel modulation. These findings underscore the importance of the K + channel pathway in the regulation of coronary vasomotor tone in pathophysiologic states.
- Coronary circulation
- Potassium channels
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine