Bradykinin induces microvascular preconditioning through the opening of calcium-activated potassium channels.
BACKGROUND
This study was designed to investigate whether the activation of calcium-activated potassium (K(Ca)) or adenosine triphosphate sensitive potassium (K(ATP)) channels are required for bradykinin-induced microvascular preconditioning.


METHODS
Isolated rabbit hearts underwent retrograde perfusion with Krebs-Henseleit buffer (KHB) followed by 60 minutes of ischemic arrest with cold crystalloid cardioplegia (CCCP). Eight CCCP hearts received no pretreatment. Six bradykinin-preconditioned hearts received a 10-minute coronary infusion of 10(-8) mol/L bradykinin-enriched KHB followed by a 5-minute recovery period before CCCP. Six hearts received both 10(-8) mol/L charybdotoxin (a K(Ca) channel blocker) and bradykinin preconditioning. Finally, 6 other hearts received 10(-5 degrees ) mol/L glibenclamide (a K(ATP) channel blocker) to bradykinin-enriched KHB. All hearts were reperfused for 30 minutes with KHB.


RESULTS
Bradykinin preconditioning significantly improved the recovery of left ventricular and microvascular function, as compared with control. On the other hand, bradykinin preconditioning significantly reduced the contractile responses to U46619, a thromboxane A2 analogue. Charybdotoxin significantly inhibited the improved recovery of bradykinin-induced left ventricular and microvascular function. Glibenclamide tended to diminish the bradykinin preconditioning-enhanced recovery of left ventricular function, but failed to affect bradykinin preconditioning-improved recovery of microvascular function.


CONCLUSIONS
Both K(Ca) and K(ATP) channels were involved partially in bradykinin-induced myocardial preconditioning. However, bradykinin induces microvascular preconditioning through the opening of K(Ca) channels rather than K(ATP) channels.
Feng
Jun
J
Department of Surgery, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA 02215, USA.
Sellke
Michelle E
ME
Ramlawi
Basel
B
Boodhwani
Munir
M
Clements
Richard
R
Li
Jianyi
J
Bianchi
Cesario
C
Sellke
Frank W
FW
D000255:Adenosine Triphosphate; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D005905:Glyburide / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008833:Microcirculation / Q000187:drug effects; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D046509:Tissue Culture Techniques; D014665:Vasodilator Agents / Q000494:pharmacology*
D024681:Potassium Channels, Calcium-Activated; D014665:Vasodilator Agents; D018999:Charybdotoxin; D000255:Adenosine Triphosphate; D001920:Bradykinin; D005905:Glyburide