title: A nimodipine-resistant Ca2+ pathway is involved in myogenic tone in a resistance artery.
abstract: After stretch, tone develops in ring segments of rabbit ear resistance arteries (75-150 micron unstretched lumen diam). This is myogenic tone, since it is not dependent on the presence of sympathetic nerves, endothelial cells, or the local release of any known vasoactive autacoids. It is sensitive to the extracellular Ca2+ concentration, and disappears in a low Ca2+ (25 microM) environment. Tone is restored immediately on the reintroduction of Ca2+ (0.1-1.6 mM). High K+-induced tone in these resistance arteries is also extracellular Ca2+-dependent. The Ca2+ ED50 of this tone is 2.45 X 10(-4) M, which is significantly lower than that for myogenic tone (Ca2+ ED50; 8.31 X 10(-4) M). Both tone moieties are influenced by inorganic Ca2+ antagonists (Mn2+ and Mg2+) and some organic Ca2+ antagonists (verapamil and diltiazem). Among all the Ca2+ antagonists studied, only Mn2+ completely inhibits myogenic tone. In contrast, myogenic tone is resistant to nimodipine (up to 10(-6) M), the most potent Ca2+ antagonist of K+-induced contraction (ID50; 1.0 X 10(-9) M). Other 1,4-dihydropyridine Ca2+ antagonists such as nifedipine and (-)-PN 200-110 selectively antagonize K+-induced contractions, whereas they do not affect the development and the maintenance of myogenic tone. The fact that the (+)-enantiomer of PN 200-110 does not have an inhibitory effect proves that the 1,4-DHP site is stereospecific. These results indicate that extracellular Ca2+ is essential for both stretch-dependent (myogenic) and K+-induced tone, and the Ca2+ entry pathways for the two tone moieties are differently influenced by dihydropyridines.
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001158:Arteries / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D017275:Isradipine; D008297:Male; D008345:Manganese / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009539:Nicotinic Acids / Q000494:pharmacology*; D009553:Nimodipine; D010069:Oxadiazoles / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D014655:Vascular Resistance; D014700:Verapamil / Q000494:pharmacology
chemical_list: D009539:Nicotinic Acids; D010069:Oxadiazoles; D008345:Manganese; D009553:Nimodipine; D014700:Verapamil; D004110:Diltiazem; D011188:Potassium; D002118:Calcium; D017275:Isradipine