Receptor-mediated C-kinase activation contributes to alpha-adrenergic tone in rat mesenteric resistance artery.
Small branches from the superior mesenteric arteries (100-200 microns outer diameter) freshly dissected from male Wistar-Kyoto (WKY) rats were mounted for tension recordings. Some arterial rings were left in physiological salt solution and used as intact arteries while others were made permeable with alpha-toxin and incubated in cytoplasmic substitution solution. The relationship between ambient [Ca2+] and tension development during various modes of activation was measured in both intact and permeable arterial rings. The effects of ryanodine and 12-O-tetradecanoyl phorbol-13-acetate (TPA) were tested. Ryanodine had no effect on the tone developed in response to noradrenaline, but tension was increased when the tissues were bathed in 80 mmol/l K+ and [Ca2+] was raised (10 mmol/l). If it is assumed that ryanodine acts exclusively to enhance the permeability of the sarcoplasmic reticulum in smooth muscle, these data suggest that noradrenaline-induced tone is partly due to inhibition of Ca2+ buffering in the sarcoplasmic reticulum. However, this action of noradrenaline is not as pronounced in the resistance arteries as it is in the rabbit aorta. 12-O-tetradecanoyl phorbol-13-acetate had no effect on the noradrenaline-induced contractions of the intact resistance arteries, but caused a large leftward shift in the relationship between tension and extracellular [Ca2+] when high-K+ depolarization was the stimulus. This increased sensitivity to extracellular [Ca2+] could not be explained by stimulation of the Ca2+ influx. Instead, application of TPA to the rings made permeable with alpha-toxin dramatically increased the myofilament sensitivity to Ca2+, as demonstrated by a shift to the left of the tension-intracellular-[Ca2+] curve.(ABSTRACT TRUNCATED AT 250 WORDS)
Drenth
J P
JP
Department of Pharmacology, University of Miami School of Medicine, Florida 33101.
Nishimura
J
J
Nouailhetas
V L
VL
van Breemen
C
C
D000818:Animals; D002118:Calcium / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009129:Muscle Tonus / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D012433:Ryanodine; D011493:Protein Kinase C; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine