Mechanisms of vasoconstriction induced by endothelin‐1 in smooth muscle of rabbit mesenteric artery.

Abstract

1. The mechanism underlying the vasoconstriction induced by endothelin-1 (ET-1) was investigated by measuring the intracellular concentration of Ca2+ ([Ca2`]1), isometric force and phosphorylation of the myosin light chain (MLC) in endothelium-denuded unskinned and ,b-escin-treated skinned smooth muscle from resistance vessels of the rabbit mesentery. The role of protein kinase C (PKC) in the action of ET-1 was studied in skinned smooth muscle using a synthetic peptide, which 5. These results suggest that ET-1 acts on the ETA receptor and increases Ca2+ influxes through an activation of the dihydropyridine-sensitive Ca2" channel, causing a longlasting and maintained contraction in resistance vessels of the rabbit mesentery. ET-1 increases Ca2+-induced MLC phosphorylation through an activation of both PKCdependent and -independent mechanisms and thus causes an increase in the sensitivity of contractile proteins to Ca2+.Endothelin is one of a family of peptides which includes a locally acting paracrine hormone rather than a endothelin-1 (ET-1), endothelin-2, endothelin-3 (ET-3) and circulating hormone (Haynes & Webb, 1993 stress, al. 1988;. ET-1 is thought to be hypoxia, growth factors and so on. Circulating

Mechanisms involved in carbachol‐induced Ca2+ sensitization of contractile elements in rat proximal and distal colon

“…Thus, although smooth muscle of the rat proximal colon possesses a mechanism of Ca 2 þ sensitization through the activation of protein kinase C, this mechanism seems not to be linked to activation of muscarinic receptors in the proximal colon. Similar results in adrenergic receptors were reported in the rabbit mesenteric artery (Yoshida et al, 1994) and the guinea pig vas deferens . On the other hand, the linkage between the muscarinic receptor and protein kinase C in the distal colon is evident in the present study.…”

Endothelin-1 Enhances Eicosanoids-Induced Coronary Smooth Muscle Contraction by Activating Specific Protein Kinase C Isoforms

“…These results are consistent with previous reports that vascular smooth muscle contraction in response to ET-1 is triggered by increases in [Ca 2ϩ ] i due to Ca 2ϩ release from the intracellular stores and Ca 2ϩ entry from the extracellular space. [27][28][29][30] ET-1 at very small and physiological concentrations (10 -11 mol/L) still caused a significant contraction of coronary smooth muscle cells that was not associated with any increases in [Ca 2ϩ ] i , suggesting activation of other mechanisms of smooth muscle contraction that may increase the myofilament force sensitivity even to basal levels of [Ca 2ϩ ] i . Although the ET-1 contraction at physiological concentrations seemed to be relatively small, this contraction could be of considerable significance because only minimal circumferential coronary vasoconstriction is often necessary to critically reduce the luminal cross-sectional area in the setting of significant coronary vasospasm.…”

Endothelin-1 Induces Contraction via a Syk-Mediated p38 Mitogen-Activated Protein Kinase Pathway in Rat Aortic Smooth Muscle

“…It has been reported that ET-1-induced contraction results from an increase of [Ca 2+ ] i and MLC phosphorylation (7). It is known, however, that changes in [Ca 2+ ] i do not always parallel the level of contraction and MLC phosphorylation (8,9).…”