Blockade or reversal of the contraction induced by calcium and adrenaline in depolarized arterial smooth muscle

Abstract

1. Mesenteric arteries immersed in a depolarizing solution contract in the presence of calcium. These contractions are proportional to the calcium concentration and are reversible. 2. Mesenteric arteries immersed in a calcium-free depolarizing solution contract in the presence of adrenaline. Under the experimental conditions reported here, this response develops only albout one-third of the contractile tension developed in polarizing solution (modified Krebs bicarbonate). 3. Cinnarizine and chlorpromazine inhilbit the contractile response to calcium and induce relaxation of depolarized muscle previously contracted by calcium; cinnarizine was 4 times more potent than chlorpromazine in such activity. 4. Chlorpromazine inhibits the response to adrenaline in lboth polarizing and calcium-free depolarizing solutions, whereas cinnarizine inhibits the response in polarizing solution but not that in calcium-free depolarizing solution. 5. The significance of these results is discussed.TIhe contractile response of vascular smooth muscle to depolarization by potassium is reduced by phenoxybenzamine, dibenamine and chlorpromazine (Bevan,

Effects of flecainide on isolated vascular smooth muscles of rat

“…The phasic component, since it persists in Ca-free medium, has been attributed to the release of Ca from intracellular stores (Hudgins & Weiss, 1968;Godfraind & Kaba, 1969). Flecainide inhibited both the tonic and phasic components of NA-induced contractions which suggests decreased Ca entry through ROCs and receptormediated Ca release from intracellular store sites, respectively.…”

Effects of propafenone on 45Ca movements and contractile responses in vascular smooth muscle

“…These results confirmed and extended previous experimental evidence showing that propafenone exhibited spasmolytic effects in vascular (Hapke & Prigge, 1976;Harder & Bellardinelli, 1980;Philipsborn et al, 1984) and non-vascular smooth muscle fibres (Hapke & Prigge, 1976;Kukovetz et al, 1977). In rat isolated aorta NA-and high K-induced contractions have been resolved into a phasic and a tonic component (Hudgins & Weiss, 1968;Godfraind & Kaba, 1969). An increase in Ca entry through receptor-operated channels (ROCs) seems to determine the tonic component of NAinduced contractions (Hudgins & Weiss, 1968;Deth & Van Breemen, 1974;Bolton, 1979), whereas both contractile responses induced by high K or by increasing Ca concentration in K-depolarized aortae are thought to be entirely dependent upon the influx of extracellular Ca through voltage-sensitive channels (VSCs) (Hudgins & Weiss, 1968;Godfraind & Kaba, 1969;Bolton, 1979).…”

“…In rat isolated aorta NA-and high K-induced contractions have been resolved into a phasic and a tonic component (Hudgins & Weiss, 1968;Godfraind & Kaba, 1969). An increase in Ca entry through receptor-operated channels (ROCs) seems to determine the tonic component of NAinduced contractions (Hudgins & Weiss, 1968;Deth & Van Breemen, 1974;Bolton, 1979), whereas both contractile responses induced by high K or by increasing Ca concentration in K-depolarized aortae are thought to be entirely dependent upon the influx of extracellular Ca through voltage-sensitive channels (VSCs) (Hudgins & Weiss, 1968;Godfraind & Kaba, 1969;Bolton, 1979). Propafenone inhibited in a concentration-dependent manner the contractile responses induced by high K depolarization or by Ca which have been used to provide a simple means of studying drugs with possible Ca entry blocking properties (Haeusler, 1972;Godfraind et al, 1986) as well as the tonic component of NAinduced responses.…”

AMP-activated Protein Kinase Phosphorylates and Desensitizes Smooth Muscle Myosin Light Chain Kinase

“…Muscle tone was measured using an isometric force transducer (25). The artery segment was incubated for 30 min in Krebs solution and thereafter stimulated with a KCl solution or with phenylephrine at concentrations ranging from 10 Ϫ9 to 10 Ϫ5 M. The KCl-depolarizing solutions were obtained by isotonic replacement of NaCl with KCl in Krebs solution (26). Tension developed was expressed as millinewtons/mm.…”