Relaxing Effect of Atrial Natriuretic Factor on Endothelin-Precontracted Vascular Strips

Mc, Bonhomme; Cantin, M.; García, Raquel Muñoz

doi:10.3181/00379727-217-rc1

Cited by 11 publications

(1 citation statement)

References 6 publications

(6 reference statements)

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“…Although inhibition of PIP2 hydrolysis by cyclic GMP can account for inhibition of the early activation of PKC by endothelin-1, cyclic GMP elevating agents have been shown to cause a reversal of the sustained or tonic phase of endothelin-l-induced contraction in vascular smooth muscle (Yanagisawa et al, 1988;Bonhomme et al, 1989;Miller et al, 1989). This suggests that cyclic GMP may also inhibit the sustained production of DAG and the late phase of PKC activation.…”

Section: Discussionmentioning

confidence: 99%

Endothelium‐derived relaxing factor inhibits the endothelin‐1‐induced increase in protein kinase C activity in rat aorta

Lang

Lewis

1991

British J Pharmacology

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1 Particulate and cytosolic protein kinase C (PKC) activity was measured in rat aortae with and without endothelium, following exposure to endothelin-1 (10-8 M) for various time intervals. 2 Endothelin-1 induced two peaks of particulate PKC activity, occurring at 30s and 10min exposure times in both endothelium-intact and endothelium-denuded preparations. Cytosolic PKC activity fell below baseline at all incubation times studied. 3 In endothelium-denuded preparations, elevation of guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels with sodium nitroprusside (10-6M) or atrial natriuretic peptide (10-6M) and, in endothelium-intact preparations with the calcium ionophore A23187 (10-6M), inhibited the activation of particulate PKC activity seen after incubation with endothelin-1 for 30s. The inhibitory effect of A23187 was prevented by prior incubation of the endothelium-intact vessels with the nitric oxide synthetase inhibitor, L-NG-nitro arginine (5 x 10-s M). 4 These results indicate that EDRF acting via cyclic GMP can inhibit the activation of PKC induced by endothelin-1 in rat aorta. Keywords: Rat aorta; EDRF; protein kinase C; endothelin; L-N0-nitro arginine IntroductionIn vascular smooth muscle, protein kinase C (PKC) is present in relatively high concentrations (Nishizuka, 1984) and is presumed to play an important role in the regulation of tone, particularly during the tonic phase of contraction (Rasmussen et al., 1987;Haller et al., 1990). Several constrictor agonists including endothelin have now been shown to cause activation and translocation of PKC from the cytosolic to the particulate fraction of vascular smooth muscle cells (Haller et al., 1990) and it has been shown that these events are responsible for the maintenance of tone during the tonic phase of contraction.Nitric oxide is now known to be the active principle of endothelium-derived relaxing factor (EDRF; Palmer et al., 1987). It induces vascular smooth muscle relaxation by the activation of soluble guanylate cyclase and elevation of intracellular levels of guanosine 3': 5'-cyclic monophosphate (cyclic GMP) (for review see Griffith et al., 1988). However, the precise mechanism whereby cyclic GMP induces smooth muscle relaxation is not fully understood. It is known that cyclic GMP inhibits phosphatidylinositol (PI) hydrolysis in vascular smooth muscle (Rapoport, 1986) and platelets (Takai et al., 1981). More recently it has been shown that in both vascular smooth muscle and endothelium this effect of cyclic GMP leads to inhibition of agonist-induced inositol 1,4,5-trisphosphate (1P3) production (Lang & Lewis, 1989;. However, this effect of cyclic GMP on IP3 production does not adequately explain the mechanism of inhibition of vascular smooth muscle tone during the tonic phase of contraction, which involves PKC activation.In the present study therefore we have investigated the effects of EDRF and other cyclic GMP elevating agents, on endothelin-1-induced activation of PKC in rat aorta. Methods Tissue preparationMale Wistar rats (250-300 g) ...

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Section: Discussionmentioning

confidence: 99%

Endothelium‐derived relaxing factor inhibits the endothelin‐1‐induced increase in protein kinase C activity in rat aorta

Lang

Lewis

1991

British J Pharmacology

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C‐type natriuretic peptides are potent dilators of shark vascular smooth muscle

et al. 1993

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Previous studies of the effects of C-type natriuretic peptides (CNP) in intact mammals have demonstrated limited hypotensive responses, in contrast to other natriuretic peptides. Our previous studies, on isolated vascular smooth muscle (VSM) from various fish species, utilizing either mammalian or non-homologous fish atrial natriuretic peptides (ANP), have demonstrated vasodilation with a relatively high sensitivity (EC50 approximately 5 nM). The recent sequencing of a C-type natriuretic peptide from the heart of the dogfish shark, Squalus acanthias, has enabled us to compare the efficacy of this peptide on aortic VSM from that species with two other CNPs (from killifish and pig), as well as rat ANP. The EC50 of dilation for sCNP, as well as kCNP and pCNP, was 0.5 nM, over 15 times lower than the EC50 of the response to rANP. These data suggest that CNP is released from the dogfish shark heart and is a circulating hormone with potent vasodilatory effects, in sharp contrast to the apparent role of CNP predominantly as a brain neuropeptide in mammals.

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Hypothetical Role of Endothelin in the Control of the Cardiovascular System

Rubanyi¹,

Shepherd²

1992

Endothelin

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Relaxing Effect of Atrial Natriuretic Factor on Endothelin-Precontracted Vascular Strips

Cited by 11 publications

References 6 publications

Endothelium‐derived relaxing factor inhibits the endothelin‐1‐induced increase in protein kinase C activity in rat aorta

Endothelium‐derived relaxing factor inhibits the endothelin‐1‐induced increase in protein kinase C activity in rat aorta

C‐type natriuretic peptides are potent dilators of shark vascular smooth muscle

Hypothetical Role of Endothelin in the Control of the Cardiovascular System

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