Responses to bradykinin are mediated by NO-independent mechanisms in the rat hindlimb vascular bed

• Published in: Pharmacological research 2004-12, Vol.50 (6), p.575-584
• Main Authors: Dabisch, Paul A., Kerut, Edmund K., Liles, John T., Wien, George, Smith, Michele, Patterson, Matthew, Mccoul, Edward D., Sears, Benjamin W., Saenz, Rodrigo, Kadowitz, Philip J.
• Format: Article
• Language: English
• Subjects: Animals; Bradykinin; Bradykinin - pharmacology; Dose-Response Relationship, Drug; Hindlimb - blood supply; Hindlimb - drug effects; Hindlimb - physiology; Male; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - physiology; Nitroprusside - pharmacology; Potassium channels; Rats; Rats, Sprague-Dawley; Vascular Resistance - drug effects; Vascular Resistance - physiology
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2004.07.001

The vasodilator response to bradykinin (BK) appears to be mediated by a number of different endothelium-derived relaxing factors (EDRFs). The EDRFs mediating the response depend on the species and vascular bed studied. The mechanism by which BK dilates the hindlimb vascular bed was investigated in the anesthetized rat. BK produced dose-dependent increases hindlimb blood flow. The NOS antagonist L-NAME had little effect on the magnitude of the increase in flow when baseline hemodynamic parameters were corrected by an NO donor infusion. However, the duration of the response was slightly shortened by L-NAME. Charybdotoxin (Chtx) and apamin nearly abolished the L-NAME resistant component of the hindlimb vasodilator response to BK, but did not affect the hindlimb vasodilator response to the sodium nitroprusside (SNP). The cyclooxygenase inhibitor meclofenamate and the K +-ATP channel blocker U37883A, in the presence of L-NAME, did not alter the vasodilator response to BK. These results suggest that a significant portion of the hindlimb vasodilator response to BK is mediated by the activation of K Ca channels, and independent of NO synthesis, cyclooxygenase products, and activation of K +-ATP channels. The present data suggest that the mechanisms mediating the vasodilator response to BK in the hindlimb vascular bed of the rat are complex, consisting of a Chtx and apamin sensitive, L-NAME resistant phase and a minor phase mediated by NO. In contrast, NO accounts for about half of the hindlimb vasodilator response to acetylcholine (ACh), with the other half of the response mediated by a Chtx and apamin sensitive mechanism. Additionally, the present results demonstrate that the NO donor infusion technique is able to compensate for the loss of basal NO production following inhibition of NOS, and to restore hemodynamic parameters to pre-L-NAME levels, making it a useful technique for the investigation of the role of NO in mediating vascular responses.