Circulatory effects of a depilatory dose of mouse epidermal growth factor in sheep.

Carter, N B; Fawcett, A. A.; Hales, J. R. S.; Moore, George T.; Panaretto, BA

doi:10.1113/jphysiol.1988.sp017236

Cited by 24 publications

(10 citation statements)

References 26 publications

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“…Gan et al (8) reported that EGF (30 mg/kg i.p.) had no significant effects on hindlimb resistance in anesthetized rats; however, these same authors and others have reported increased tone (vasoconstriction) in arterial strips from rats treated with EGF (3,4,26). EGF is also reported to induce vasodilatation in a number of vascular beds (femoral, mesenteric, coronary, and renal) in anesthetized dogs and EGF (gg/kg) sheep (5,25,27).…”

Section: Discussionmentioning

confidence: 91%

Hemodynamic effects of epidermal growth factor in conscious rats and monkeys.

Keiser¹,

Ryan²

1996

Proc. Natl. Acad. Sci. U.S.A.

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The therapeutic application of growth factors to human disease has become closer to reality with the advent of faster means of synthesizing these molecules and novel drug delivery strategies. Epidermal growth factor (EGF) belongs to a large family of molecules with the ability to modulate growth. Purified extracts of EGF have been used clinically to modulate gastrointestinal secretion of hormones and accelerate healing. EGF is also reported to have both vascular smooth muscle contractile and relaxing activity. Cardiovascular studies were performed with the bioactive 48-amino acid fragment of human EGF in rodents and primates to determine the effects of EGF on blood pressure and heart rate in conscious animals. Intravenous infusion of EGF induced an initial pressor response in rats followed by a prolonged decrease in blood pressure. In contrast, in monkeys, EGF had dose-related blood pressure-lowering effects only; significant hypotension was observed at doses ranging from 3 to 300 ,lg/kg i.v. Hypotension was associated with modest tachycardia.in both species. To our knowledge, this is the first report of hemodynamic effects of EGF in primates, and it clearly documents that the mitogenic role of growth factors such as EGF is but one aspect of their physiology.In addition to the well-recognized mitogenic activity of growth factors, there is an increasing understanding of their vasoactive effects. Epidermal growth factor (EGF) belongs to a large family of molecules with the ability to modulate growth (1, 2). EGF is also reported to have both vascular smooth muscle contractile and relaxing activity in vitro (3-6). Berk et al. (4) reported that EGF produced contractions in isolated rat aorta that were roughly 40% of the maximal response to angiotensin; time to peak tension was relatively short (2-3 min). In contrast, Namiki and Akatsuka (7) reported that EGF relaxed isolated rat aortic strips; Muramatsu et al. (6) reported similar findings in isolated canine mesenteric arteries. Divergent results have also been obtained from in vivo studies. Gan et al. (8) reported that EGF had no effect on regional hemodynamics in anesthetized rats; however, regional bed vasodilatation was observed in the anesthetized dog (5). Thus, there is remarkable species heterogeneity in the vasoactive properties of EGF.A number of growth factors are receiving increased attention as potential therapeutic agents. EGF, hepatocyte growth factor, and insulin-like growth factor are reported to protect against or ameliorate renal ischemic injury in a variety of models (9-13), although these effects show some species variation (14). EGF is also reported to accelerate gastric ulcer healing and inhibit gastric acid secretion (15-17). The potential therapeutic effects of EGF have been of interest for a number of years. Partially purified EGF preparations extracted from human urine (referred to as urogastrone) have been administered to humans as early as the mid-1970s to modulate gastric acid secretion (18)(19)(20)(21). Using gene transfer techni...

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Section: Discussionmentioning

confidence: 91%

Hemodynamic effects of epidermal growth factor in conscious rats and monkeys.

Keiser¹,

Ryan²

1996

Proc. Natl. Acad. Sci. U.S.A.

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“…EGF is known to have specific vasodilatory effects in the mucosa of the alimentary tract in sheep, and leads to direct relaxation of isolated rabbit mesenteric arteries through activation of EGFR 37, 38. Using a rat ethanol/toxicity model, EGF protected gastric mucosa from ethanol-induced mucosal injury via an increase in gastric blood flow 39.…”

Section: Discussionmentioning

confidence: 99%

Heparin-Binding EGF-Like Growth Factor Increases Intestinal Microvascular Blood Flow in Necrotizing Enterocolitis

Radulescu

Zorko

et al. 2009

Gastroenterology

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Background & Aims-Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates. Although the exact etiology remains unknown, decreased intestinal blood flow is thought to play a critical role. We have shown that heparin-binding EGF-like growth factor (HB-EGF) protects the intestines from injury in a rodent model of NEC. Our current goal was to assess the effect of HB-EGF on intestinal microvascular blood flow and intestinal injury in rat pups subjected to experimental NEC.

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“…In this study, we also observed EGFR immunoreactivity in some blood vessels, but as there levels of pEGFR always appeared low, the functional role of these receptors is unknown. EGF is, however, known to increase blood flow in several tissues [32,33] and previous studies have indicated that castrationinduced prostate glandular involution is, at least in part, caused by an early drop in prostate blood flow and subsequent ischemic cell death of prostate epithelial cells [34][35][36]. The possibility that gefitinib may affect the vasculature directly or indirectly by decreasing the synthesis of vascular regulators like bFGF, IL-8, TGF-a, and VEGF [6] in prostate epithelial and stroma cells, can thus not be excluded.…”

Section: Discussionmentioning

confidence: 99%