Insulin-Like Growth Factor-I Decreases Mean Blood Pressure and Selectively Increases Regional Blood Flow in Normal Rats

Pete, Gina; Hu, Yuange; Walsh, Mary; Sowers, James R.; Dunbar, Joseph C.

doi:10.3181/00379727-213-44049

Cited by 45 publications

(25 citation statements)

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“…The cardioprotective effects of GH may have been mediated by an elevation of plasma IGF-I levels. In fact, it has been shown that IGF-I stimulates nitric oxide (NO) release from cultured endothelial cells, and NO is an important regulator of vascular function (37). In contrast, hexarelin did not stimulate plasma levels of IGF-I.…”

Section: Discussionmentioning

confidence: 98%

Growth Hormone-Independent Cardioprotective Effects of Hexarelin in the Rat1

et al. 1999

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We previously reported that induction of selective GH deficiency in the rat exacerbates cardiac dysfunction induced by experimental ischemia and reperfusion performed on the explanted heart. In the same model, short-term treatment with hexarelin, a GH-releasing peptide, reverted this effect, as did GH. To ascertain whether hexarelin had non-GH-mediated protective effects on the heart, we compared hexarelin and GH treatment in hypophysectomized rats. Hexarelin (80 g/kg sc), given for 7 days, prevented exacerbation of the ischemiareperfusion damage induced by hypophysectomy. We also demonstrate that hexarelin prevents increases in left ventricular end diastolic pressure, coronary perfusion pressure, reactivity of the coronary vasculature to angiotensin II, and release of creatine kinase in the heart perfusate. Moreover, hexarelin prevents the fall in prostacyclin release and enhances recovery of contractility. Treatment with GH (400 g/kg sc) produced similar results, whereas administration of EP 51389 (80 g/kg sc), another GH-releasing peptide that does not bind to the heart, was ineffective.In conclusion, we demonstrate that hexarelin prevents cardiac damage after ischemia-reperfusion, and that its action is not mediated by GH but likely occurs through activation of specific cardiac receptors. (Endocrinology 140: 4024 -4031, 1999)

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Section: Discussionmentioning

confidence: 98%

Growth Hormone-Independent Cardioprotective Effects of Hexarelin in the Rat1

et al. 1999

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“…Short-term injection of IGF-1 decreased mean arterial pressure, and this effect was inhibited by preinfusion of an NO inhibitor, indicating that the decrease in blood pressure in response to IGF-1 is mediated by NO. 138 A significant elevation of arterial pressure was also observed in mice homozygous for a site-specific insertional mutation in exon 3 of IGF-1. 139 Peripheral resistance and systolic blood pressure were increased in liver-specific IGF-1 knockout mice.…”

Section: Hypertensionmentioning

confidence: 97%

Expression, Regulation, and Function of IGF-1, IGF-1R, and IGF-1 Binding Proteins in Blood Vessels

Delafontaine

Song

2004

ATVB

480

374

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Abstract-The vascular insulin-like growth factor (IGF)-1 system includes the IGFs, the IGF-1 receptor (IGF-1R), and multiple binding proteins. This growth factor system exerts multiple physiologic effects on the vasculature through both endocrine and autocrine/paracrine mechanisms. The effects of IGF-1 are mediated principally through the IGF-1R but are modulated by complex interactions with multiple IGF binding proteins that themselves are regulated by phosphorylation, proteolysis, polymerization, and cell or matrix association. During the last decade, a significant body of evidence has accumulated, indicating that expression of the components of the IGF system are regulated by multiple factors, including growth factors, cytokines, lipoproteins, reactive oxygen species, and hemodynamic forces. In addition, cross-talk between the IGF system and other growth factors and integrin receptors has been demonstrated. There is accumulating evidence of a role for IGF-1 in multiple vascular pathologies, including atherosclerosis, hypertension, restenosis, angiogenesis, and diabetic vascular disease. This review will discuss the regulation of expression of IGF-1, IGF-1R, and IGF binding proteins in the vasculature and summarize evidence implicating involvement of this system in vascular diseases.

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“…Moreover, there is an increasing body of evidence demonstrating that IGF-I exerts multiple vascular effects through endocrine, autocrine, and paracrine mechanisms (3). Because IGF-I induces NO production in endothelial cells, it is a potent mediator of vasodilation (38) and is capable of lowering systemic blood pressure (30). IGF binding protein 1 (IGFBP1) is a carrier protein that binds to IGF-I with high affinity and therefore is placed in a critical regulatory position between IGF-I and its receptor.…”

Section: Discussionmentioning

confidence: 99%

A physiogenomic approach to study the regulation of blood pressure

Westhoff¹,

Scheid²,

Tölle³

et al. 2005

Physiological Genomics

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van der Giet. A physiogenomic approach to study the regulation of blood pressure. Physiol Genomics 23: 46 -53, 2005. First published June 7, 2005; 10.1152/physiolgenomics.00077.2005.-Several vasoregulatory systems including the renin-angiotensin system, sympathetic vasoregulation, and cytokine release have been studied extensively. The aim of the present study was to establish a physiogenomic screening model for differentially expressed genes in the regulation of blood pressure that might give a hint as to new vasoregulatory mechanisms. We induced acute hypotension in normotensive rats, assuming that vasoregulatory systems will counteract hypotension. Microarray transcriptome analysis was performed from kidneys 6 h after the induction of acute hypotension. The results were confirmed by real-time PCR. Six functionally known genes (Igfbp1, Xdh, Sult1a1, Mawbp, Por, and Gstm1) and two expressed sequence tages (BI277460 and AI411345) were significantly upregulated. Four of these genes (Igfbp1, Xdh, Por, and Gstm1) have well-characterized functions in the cardiovascular system. The proteins corresponding to Xdh, Por, and Gstm1 are involved in the metabolism of reactive oxygen species (ROS). Because ROS can mediate endothelial dysfunction, we measured the aortic dilatory capacity in thoracic aortic rings. Indeed, vasodilator potency to acetylcholine was largely diminished in hypotensive animals, whereas sodium nitroprusside induced equivalent vasodilations in normotensive and hypotensive animals. The vasodilator potency of the endothelium was partially restored by the superoxide scavenger tiron. Hence, acute hypotension induces a diminished vasodilator potency of the endothelium due to an accelerated degradation of nitric oxide by ROS. The present physiogenomic approach is capable of detecting vasoregulatory mechanisms and may provide deeper insight into the genetics and physiology of blood pressure regulation.geneticsendotheliummicroarrayreactive oxygen species VASCULAR TONE is regulated by a dynamic balance of local chemical, neural, and humoral mechanisms. The systemic regulatory mechanisms synergize with local mechanisms and adjust specific vascular responses in different vascular beds. Because of its central role in volume and vascular resistance regulation (e.g., the renin-angiotensin-aldosterone system), the kidney constitutes a major component in the systemic control of blood pressure (35). Local control of blood pressure is largely affected by chemical conditions (pH, O 2 tension, and CO 2 tension) and the paracrine properties of the endothelium. The vascular endothelium releases several vasodilator and vasoconstrictor substances including prostaglandins, thromboxanes, nitric oxide (NO), endothelins, complex nucleotides, and reactive oxygen species (ROS) (17,29,40). At present, there is increasing evidence that vascular cytochrome P-450 metabolites of arachidonic acid (20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acid) play an important role in the control of vascular tone and in the long-term cont...

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Insulin-Like Growth Factor-I Decreases Mean Blood Pressure and Selectively Increases Regional Blood Flow in Normal Rats

Cited by 45 publications

References 0 publications

Growth Hormone-Independent Cardioprotective Effects of Hexarelin in the Rat1

Growth Hormone-Independent Cardioprotective Effects of Hexarelin in the Rat1

Expression, Regulation, and Function of IGF-1, IGF-1R, and IGF-1 Binding Proteins in Blood Vessels

A physiogenomic approach to study the regulation of blood pressure

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