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Agonist‐induced periodic vasomotion in rat isolated pulmonary artery
Author(s) -
Burke Megan M.,
Bieger Detlef,
Tabrizchi Reza
Publication year - 2011
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2010.00878.x
Subject(s) - vasomotion , carbenoxolone , pinacidil , endocrinology , tetraethylammonium , agonist , chemistry , medicine , biophysics , inhibitory postsynaptic potential , chelerythrine , gap junction , vasodilation , intracellular , biology , biochemistry , glibenclamide , receptor , protein kinase c , enzyme , potassium , organic chemistry , diabetes mellitus
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 n m ) and the L channel agonist S (‐)‐Bay K 8644 (3–20 n m ). 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 n m ) increased off‐cycle length without change in slow‐wave amplitude. Conversely, tetraethylammonium (1.0–3.0 m m ) augmented the latter without affecting periodicity. Carbenoxolone (10 μ m ) 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.