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The involvement of ATP‐sensitive potassium channels in β 2 ‐adrenoceptor agonist‐induced vasodilatation on rat diaphragmatic microcirculation
Author(s) -
Chang HanYu
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701192
Subject(s) - cromakalim , chemistry , salbutamol , glibenclamide , vasodilation , endocrinology , medicine , isoprenaline , terbutaline , forskolin , agonist , potassium channel , microcirculation , sodium nitroprusside , pinacidil , stimulation , nitric oxide , receptor , asthma , diabetes mellitus
The effects of glibenclamide (GLB), a blocker of ATP‐sensitive potassium (K ATP ) channels, on diaphragmatic microcirculation in male Sprague‐Dawley rats were assessed under basal conditions and after β 2 ‐adrenoceptor‐agonist stimulation. In addition, forskolin was used to bypass β‐adrenoceptors and GTP‐binding proteins (G‐protein) to explore the possible mechanism of GLB effects. For comparison, the relationships between K ATP channel activity and cyclic GMP‐mediated vasodilator responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were also assessed. Male Sprague‐Dawley rats were anaesthetized with urethane and mechanically ventilated. The left hemi‐diaphragm of each rat was prepared and microvascular blood flow (Q LDF ) was recorded with laser‐Doppler flowmetry during continuous superfusion with bicarbonate‐buffered, prewarmed Ringer solution. The drugs were topically applied to the surface of the hemi‐diaphragm. Salbutamol (0.32–32 μ M ), terbutaline (0.32 μ M –0.32 μ M ) and forskolin (0.32–10 μ M ) each elicited a concentration‐dependent increase in Q LDF . Baseline microvascular blood flow was unaffected by a 30 min suffusion of 1 μ M GLB (295±51 mV vs 325±62 mV, P =0.738). The vasodilator response elicited by salbutamol (0.32 μ M , 1 μ M and 3.2 μ M ), was significantly attenuated by a 30 min superfusion with 1 μ M GLB; this salbutamol‐induced vasodilatation was mediated via an interaction with β‐adrenoceptor receptors, as in other experiments it was greatly inhibited by 30‐min superfusion with propranolol (10 μ M ). Similarly, following 30‐min superfusion with GLB (1 μ M ), the terbutaline (1 μ M , 3.2 μ M and 10 μ M )‐induced vasodilator response was almost abolished and the vasodilator responses induced by incremental concentrations of forskolin (0.32 μ M , 1 μ M and 3.2 μ M ) were also significantly attenuated. Cromakalim (1.5 μ M , 3 μ M and 3.2 μ M ) produced an increase of Q LDF in a dose‐dependent manner, which was virtually abolished by GLB (1 μ M ). In contrast, the vasodilator responses induced by acetylcholine (32 μ M , 0.1 m M , and 0.32 m M ) or sodium nitroprusside (3.2 μ M , 10 μ M and 20 μ M ) were independent of GLB (1 μ M ). In conclusion, K ATP channels may be functional, but tonically inactive in the resting diaphragmatic microcirculation and the vasodilator effect of β 2 ‐adrenoceptor agonists may be partly mediated by K ATP channels; the activation of K ATP channels may involve the accumulation of cyclic AMP in vascular smooth muscle cells.