Pharmacological investigation of signaling mechanisms contributing to phasic and tonic components of the contractile response of rat arteries to noradrenaline.
The mechanisms contributing to the contractile responses to two different concentrations of noradrenaline (NA) in rat aorta and mesenteric artery were compared using nifedipine, which inhibits calcium influx through dihydropyridine-sensitive channels, ryanodine, which depletes intracellular calcium stores, and calphostin C, which inhibits protein kinase C (PKC). Both submaximal and maximal concentrations of NA induced a biphasic response in aorta and mesenteric artery, with an early fast phase and a later sustained tonic component. Calcium release from intracellular stores contributed to the phasic component of contraction to both concentrations of NA in aorta, although to a greater extent to the submaximal concentration. In aorta, inhibiting both intracellular calcium release and calcium influx through dihydropyridine-sensitive channels simultaneously or inhibiting PKC activity alone significantly reduced the tonic response to a maximal concentration of NA. However, the tonic response to a submaximal concentration of NA in aorta was significantly inhibited only when intracellular calcium stores were depleted with ryanodine. In mesenteric artery, the phasic response to a maximal concentration of NA was significantly depressed only when both calcium influx and intracellular calcium release were inhibited simultaneously. However, the phasic response to a submaximal concentration of NA was significantly inhibited by blocking calcium influx alone, but not by blocking intracellular calcium release alone. The tonic component of the contractile response to both concentrations of NA in mesenteric artery appeared to be mediated in part by calcium from both intracellular and extracellular sources.(ABSTRACT TRUNCATED AT 250 WORDS)
Weber
L P
LP
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Chow
W L
WL
Moshenko
J
J
Belsher
S
S
MacLeod
K M
KM
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction; D013997:Time Factors
D012433:Ryanodine; D009543:Nifedipine; D009638:Norepinephrine