Related Experiment Videos
Influence of lemakalim on the pulmonary vascular bed of the cat
J S Hood1, T J McMahon, P J Kadowitz
1Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Insights
Lemakalim is a potent pulmonary vasodilator that works by activating a specific K+ATP channel. This finding is significant for understanding pulmonary vascular regulation and potential treatments.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Ion Channel Function
Background:
- Pulmonary vascular tone regulation is crucial for maintaining blood flow and oxygenation.
- ATP-sensitive potassium (K+ATP) channels play a role in vascular smooth muscle function.
- Understanding novel vasodilators is key to managing pulmonary hypertension.
Purpose of the Study:
- To investigate the pulmonary vascular effects of the K+ATP channel opener, lemakalim.
- To compare the potency of lemakalim with cromakalim in pulmonary vasodilation.
- To determine the role of glybenclamide-sensitive K+ATP channels in mediating these responses.
Main Methods:
- Intact-chest cat model with constant flow conditions.
- Intralobar injections of lemakalim and cromakalim.
- Administration of glybenclamide to block K+ATP channels.
- Measurement of lobar arterial pressure and left atrial pressure.
Main Results:
- Lemakalim caused dose-related decreases in lobar arterial pressure.
- Lemakalim was approximately three times more potent than cromakalim as a pulmonary vasodilator.
- Glybenclamide blocked lemakalim and cromakalim-induced vasodilation but not responses to acetylcholine or VIP.
- Glybenclamide reduced calcitonin gene-related peptide (CGRP) responses.
Conclusions:
- Lemakalim exhibits potent pulmonary vasodilator activity.
- Pulmonary vasodilation by lemakalim is mediated by glybenclamide-sensitive K+ATP channels.
- These findings highlight the therapeutic potential of K+ATP channel openers in pulmonary vascular disorders.
Abstract:
Pulmonary vascular responses to the K+ATP channel opener, lemakalim, were investigated in the intact-chest cat under constant flow conditions. When tone in the pulmonary vascular bed was elevated, intralobar injections of lemakalim caused dose-related decreases in lobar arterial pressure without changing left atrial pressure. Lemakalim was approximately 3-fold more potent than cromakalim in dilating the pulmonary vascular bed, and pulmonary vasodilator responses to these K+ATP channel openers were blocked by the K+ATP channel blocking agent, glybenclamide. Glybenclamide had no significant effect on pulmonary vasodilator responses to acetylcholine or vasoactive intestinal peptide (VIP) but decreased responses to calcitonin gene-related peptide (CGRP). These data show that lemakalim has potent pulmonary vasodilator activity and suggest that responses are due to activation of a glybenclamide-sensitive K+ATP channel.