Pharmacological investigation of signaling mechanisms contributing to phasic and tonic components of the contractile response of rat arteries to noradrenaline

Abstract

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)

Role of G_S Proteins in Hypoxic Constriction of Sheep Pulmonary Artery Rings

“…We also used NaF to explore the contribution of G proteins. NaF is a nonselective activator of G proteins and its effect does not involve the participation of cell surface receptors [13]. In our study, hypoxia-induced contraction was not present in NaF-precontracted artery rings.…”

Altered circulating hormone levels, endothelial function and vascular reactivity in the testicular feminised mouse

“…Addition of mmol/l concentrations of extracellular KCl disrupts the potassium concentration gradient across the smooth muscle cell membrane, causing the membrane to become depolarised, which activates voltage-operated calcium channels (VOCCs) (43). In contrast, NA elicits smooth muscle contraction via alpha-1 adrenoceptor stimulation, which results in G-protein coupled activation of receptor-operated calcium channels (ROCCs) (44). The fact that the response to NA was not affected but the response to KCl was significantly reduced in vessels harvested from Tfm mice would suggest that the function of ROCCs is unaffected but the function of VOCCs is impaired.…”

Noradrenaline‐induced changes in intracellular Ca2+ and tension in mesenteric arteries from diabetic rats

“…The increased reactivity of diabetic arteries to α 1 ‐adrenoceptor stimulation was found to be largely dependent on the presence of extracellular Ca 2+ but there was also an apparent increased release of intracellular Ca 2+ in response to high concentrations of agonist (Abebe et al ., 1990; 1994). The initial rapid component of the contractile response to NA is partially dependent on Ca 2+ released from inositol 1,4,5 trisphosphate (IP 3 )‐sensitive intracellular stores (Watras et al ., 1989; Ferris & Snyder, 1992; Weber et al ., 1995), and we have found that the breakdown of [ 32 P]‐phosphatidylinositol 4,5‐bisphosphate, and the production of [ 3 H]‐inositol phosphates and IP 3 were enhanced in response to maximal stimulation by NA in diabetic arteries (Abebe & Macleod, 1991; 1992). We therefore proposed that the increased levels of IP 3 promote greater release of Ca 2+ from intracellular stores, thereby contributing to higher cytosolic Ca 2+ levels and the enhanced contractile responses of diabetic arteries to NA.…”