Insulin-like growth factor I inhibits induction of nitric oxide synthase in vascular smooth muscle cells.

Abstract

Experiments were designed to examine whether or not insulin-like growth factor I (IGF-I), which is produced by vascular cells in response to injury, affects the production of nitric oxide evoked by the inducible nitric oxide synthase in cultures of smooth muscle cells from the rat aorta. Nitric oxide production was assessed indirectly by the measurement of nitrite accumulation and nitric oxide synthase activity by determining the formation of L-citrulline from L-arginine. Nitric oxide synthase was induced in vascular smooth muscle cells that had been exposed to interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha). IGF-I inhibited, in a concentration-dependent manner, the production of nitrite and L-citrulline evoked by IL-1 beta or TNF-alpha. The inhibition caused by IGF-I required the presence of the growth factor during the induction of nitric oxide synthase. Two IGF-I-related proteins, IGF-II and insulin, also inhibited, but to a smaller extent, the release of nitrite and the formation of L-citrulline stimulated by IL-1 beta. Under bioassay conditions, the perfusates from columns containing IL-1 beta-treated smooth muscle cells relaxed rings of rat aorta without endothelium that had been contracted with phenylephrine; these relaxations were reversed by nitro-L-arginine. Addition of IL-1 beta-treated vascular smooth muscle cells to indomethacin-treated platelets inhibited their aggregation to thrombin; methylene blue prevented this inhibition. Control smooth muscle cells or cells exposed to IGF-I alone did not have such effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Local l -Arginine Delivery After Balloon Angioplasty Reduces Monocyte Binding and Induces Apoptosis

“…18 This induction of iNOS in vascular smooth muscle cells is transient because of its downregulation by mitogens activated after vascular injury. 19 Long-term oral L-arginine supplementation 10 and single intramural administration of L-arginine 11 chronically enhance vascular NO generation, resulting in improved vasomotion and inhibition of lesion formation in hypercholesterolemic rabbits. In the present study, we dem- …”

A transferable, beta‐naphthoflavone‐inducible, hyperpolarizing factor is synthesized by native and cultured porcine coronary endothelial cells.

“…After 4-6 days the explanted smooth muscle cells had grown to confluence and the tissue piece was carefully removed from the coverslip. Culture of rat aortic smooth muscle cells Rat aortic smooth muscle cells were isolated and cultured as described (Schini, Catovsky, Schray-Utz, Busse & Vanhoutte, 1994 (Horn & Marty, 1988) of the patch-clamp technique (Hamill, Marty, Neher, Sakmann & Sigworth, 1981). The patch pipettes used had an input resistance of 8-10 MtQ when filled with standard KCl solution.…”

Nitric oxide synthases in vascular cells

“…after balloon catheter injury: Joly et al 1992) is likely to be regulated locally by factors either generated from the circulating blood or released from vascular cells (Table 2). This idea is supported by the fact that platelet-derived growth factor, transforming growth factor ,#, insulin-like growth factor, angiotensin II and thrombin prevent the synthesis of nitric oxide evoked by cytokines in cultured vascular smooth muscle cells (Junquero, Schini, Scott-Burden & Vanhoutte, 1992;Schini, Durante, Elizondo, Scott-Burden, Junquero, Schafer & Vanhoutte, 1992;Schini, Catovsky, Durante, Scott-Burden, Schafer & Vanhoutte, 1993;Nakayama, Kawahara, Tsuda, Okuda & Yokoyama, 1994;Schini et al 1994). On the other hand, an enhanced release of nitric oxide is observed in the presence of epidermal growth factor, basic fibroblast growth factor and plasmin (Scott-Burden et al 1992;Durante, Schini, Catovsky, Kroll, Vanhoutte & Schafer, 1993).…”

“…None of these vasoactive factors alone induce nitric oxide release. The downregulation of nitric oxide synthesis by injury-derived factors requires the presence of the factors during the early phase of induction and is associated with an impaired expression of the inducible nitric oxide synthase mRNA (Scott-Burden, Elizondo, Ge, Boulanger & Vanhoutte, 1993;Nakayama et al 1994;Perrella, Yoshizumi, Fen, Tsai, Hsieh, Kourembanas & Lee, 1994;Schini et al 1994). In addition, an impaired expression of GTP cyclohydrolase I resulting in lower intracellular levels of biopterin, an essential cofactor for the catalytic activity of nitric oxide synthase, may also help to explain the inhibitory effect of transforming growth factor , on cytokine-evoked nitric oxide synthesis .…”