Melatonin potentiates NE-induced vasoconstriction without augmenting cytosolic calcium concentration.
Because little is known of the intracellular mechanisms involved in the vasoconstrictor effect of melatonin (Mel), we examined the in vitro effects of Mel by using perfused cylindrical segments of the rat tail artery loaded with the intracellular Ca(2+) concentration ([Ca(2+)](i))-sensitive fluorescent dye, fura 2. Mel (10(-14) to 10(-4) M) had no effect on baseline perfusion pressure or [Ca(2+)](i) but increased, at submicromolar concentrations, the vasoconstrictor effect of norepinephrine (NE) (P = 0.0029). Mel did not modify NE-induced [Ca(2+)](i) mobilization, and thus the [Ca(2+)](i) sensitivity of NE-induced contraction increased in the presence of Mel. Mel consistently increased KCl-induced vasoconstriction and [Ca(2+)](i) sensitivity of contraction, but differences were not statistically significant. In conclusion, Mel increases the [Ca(2+)](i) sensitivity of vasoconstriction evoked by NE suggesting that Mel may amplify endogenous vasoconstrictor responses to sympathetic outflow.
Vandeputte
C
C
Laboratoire de Pharmacologie Cardiovasculaire, EA 3116, Faculté de Pharmacie, UHP-Nancy 1, 54001 Nancy Cedex, France.
Giummelly
P
P
Atkinson
J
J
Delagrange
P
P
Scalbert
E
E
Capdeville-Atkinson
C
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004357:Drug Synergism; D066298:In Vitro Techniques; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013623:Tail / Q000098:blood supply; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000975:Antioxidants; D014662:Vasoconstrictor Agents; D011189:Potassium Chloride; D008550:Melatonin; D002118:Calcium; D009638:Norepinephrine