Agonist-induced periodic vasomotion in rat isolated pulmonary artery.
Vasomotion is linked to the rapid oscillations of intracellular calcium levels. In rat pulmonary artery, this activity can manifest as a slow periodic on-off pattern, the timing of which depends on the type and intensity of pharmacological stimuli employed. In this study, we have sought to characterize a slow-wave vasomotor activity pattern induced in isolated arterial ring preparations by simultaneous exposure to the α(1) -adrenoceptor agonist phenylephrine (1-10 nm) and the L channel agonist S(-)-Bay K 8644 (3-20 nm). Treated tissues responded with a stable on-off pattern of vasomotion persisting for >5 h at 5-6 cycles/h. In intact rings, this response was suppressed by methacholine and restored or enhanced by N(ω) -nitro-l-arginine methyl ester. Analogous inhibitory effects were obtained with high Mg(2+) , 8-Br-cGMP (but not 8-Br-cAMP), riluzole, ryanodine, chelerythrine, and fasudil. Pinacidil (30 nm) increased off-cycle length without change in slow-wave amplitude. Conversely, tetraethylammonium (1.0-3.0 mm) augmented the latter without affecting periodicity. Carbenoxolone (10 μm) abolished slow-wave activity, while raising basal tone and inducing random phasic activity. In endothelium-denuded rings, the threshold of agonist-induced slow-wave vasomotion was lowered and a similar inhibitory effect obtained with carbenoxolone. In conclusion, the slow-wave pattern of vasomotion described here is (i) subject to inhibitory modulation by endothelial NO and an array of voltage-gated and leak K conductances yet to be fully characterized; (ii) dependent on Ca(2+) from both extracellular and sarcoendoplasmatic sources; (iii) controlled by kinase (Rho and PKC)-mediated regulation of myosin light chain phosphatase; and (iv) synchronized via intermyocyte gap junctions.
Burke
Megan M
MM
Division of BioMedical Sciences, Faculty of Medicine, Health Science Centre, Memorial University, St. John's, NL A1B 3V6, Canada.
Bieger
Detlef
D
Tabrizchi
Reza
R
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002229:Carbenoxolone / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D014666:Vasomotor System / Q000502:physiology*
D058646:Adrenergic alpha-1 Receptor Agonists; D053119:Benzophenanthridines; D002120:Calcium Channel Agonists; D015221:Potassium Channels; D047428:Protein Kinase Inhibitors; D016210:Methacholine Chloride; D012433:Ryanodine; D010656:Phenylephrine; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D019789:Tetraethylammonium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020110:Pinacidil; D019782:Riluzole; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C016299:chelerythrine; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D006152:Cyclic GMP; D002229:Carbenoxolone; C049347:fasudil; D019331:NG-Nitroarginine Methyl Ester