Actions of calcium antagonists on pre- and postjunctional effects of neuropeptide Y on human peripheral blood vessels in vitro.
The mechanisms underlying the contractile effects of neuropeptide Y (NPY) in relation to those of noradrenaline (NA) on small human blood vessels were studied in vitro. NPY caused contractions of mesenteric veins, renal and skeletal muscle arteries but not of mesenteric arteries. NPY was about 5- to 10-fold more potent than NA. The maximal contractile responses to NPY (5 X 10(-7) M) were 38 +/- 4, 37 +/- 8 and 95 +/- 16% of the response evoked by NA 10(-5) M in the mesenteric vein, renal and skeletal muscle arteries respectively. The NPY effects were resistant to adrenoceptor antagonists. The calcium antagonist nifedipine reduced the effect of NA but not the contractile response to NPY on mesenteric veins. Nifedipine and felodipine reduced the contractile response to both NA and NPY on renal and skeletal muscle arteries. In contrast to the contractile effects of K+, the responses to NPY and NA were largely uninfluenced by changes in extracellular Ca2+ concentrations. Nifedipine still inhibited the NPY contractions in a Ca2+-free medium while high extracellular Ca2+ (7.5 mM) partly reduced the nifedipine effect. NPY reduced the nerve stimulation-evoked [3H]NA overflow from the mesenteric veins via a nifedipine resistant mechanism. The stable analogue alpha, beta-methylene adenosine triphosphate (mATP) was more potent than ATP and had nifedipine-sensitive contractile effects similar to those of NA on the human blood vessels without influencing the nerve-evoked [3H]NA efflux. In conclusion, NPY exerts a potent nifedipine-sensitive vasoconstrictor activity, especially on human skeletal muscle arteries in vitro, although the influx of extracellular calcium may not be a crucial mechanism. The NPY-induced contractions of mesenteric veins and the inhibition of nerve-evoked [3H]NA efflux seem to be mediated via nifedipine resistant messenger systems.
D001158:Arteries; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D008642:Mesenteric Veins / Q000187:drug effects / Q000378:metabolism; D009132:Muscles / Q000098:blood supply; D009478:Neuropeptide Y / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology; D012077:Renal Artery / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D009478:Neuropeptide Y; D009543:Nifedipine; D009638:Norepinephrine