Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor-I (IGF-I) is an endocrine and autocrine/paracrine growth factor. Recently, we have demonstrated that interrenal aortic coarctation in the rat increases IGF-I mRNA levels in the thoracic aorta, consistent with a role for this mitogen in hypertensive vascular remodeling. The effects of IGF-I are modulated by several IGF binding proteins including IGFBP-3, the main circulating carrier of IGF-I, and IGFBP-4, the main IGF binding protein produced by vascular smooth muscle cells in vitro. To obtain insights into the regulation of IGF-I and more specifically to study potential changes in IGF binding proteins in high-renin hypertension, we studied male Sprague-Dawley rats that had undergone abdominal aortic coarctation. Compared with sham-operated rats, the study rats showed a rapid increase in IGFBP-4 mRNA levels in the hypertensive (thoracic) aorta, reaching a plateau at 3 days (2.5-fold increase) and persisting for at least 14 days. In striking contrast, IGFBP-4 mRNA decreased slightly in the normotensive (abdominal) aorta at 14 days. IGFBP-3 mRNA levels did not change in either vascular bed after coarctation. Study of hepatic tissue indicated that in coarcted rats IGFBP-4 and IGFBP-3 mRNA levels decreased transiently (approximately 50% at 7 days compared with sham). Circulating IGF-I in coarcted animals decreased slightly (P = .08), and Western ligand analysis indicated that circulating levels of IGF binding proteins were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Dec
PMID:Hypertension increases insulin-like growth factor binding protein-4 mRNA levels in rat aorta. 752 94

1. Growth hormone may influence cardiac growth during post-natal maturation or in response to hypertension, and the growth-hormone deficient dwarf rat model offers an opportunity to study this question. 2. We compared the blood pressure and heart weight of dwarf rats and Fischer (F344) control rats in early adulthood, after two hypertensive stimuli: unilateral renal ischaemia (two-kidney, one-clip) or the administration of deoxycorticosterone acetate and saline drinking fluid. 3. In untreated animals at 13 weeks of age the body weight of dwarf rats was significantly less than that of F344 rats, but the mean arterial pressure was similar. Although the hearts of dwarf rats were smaller than those of F344 rats, the heart weight/body weight ratio was significantly greater in dwarf rats. 4. Both dwarf and F344 rats developed similar hypertensive mean arterial pressures 5 weeks after left renal artery clipping or treatment with deoxycorticosterone acetate salt. The heart weights of hypertensive dwarf and F344 rats were equivalent, indicating a proportionally greater increase in cardiac size in dwarf rats for the same rise in blood pressure. 5. The plasma insulin-like growth factor-I level was markedly lower in dwarf than in F344 rats, and hypertension did not have any significant effects on these levels. 6. These findings indicate that the developmental increase in blood pressure and heart size in growing animals and the adaptive cardiac hypertrophy accompanying hypertension are not affected by growth hormone deficiency.
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PMID:Hypertension and cardiac hypertrophy in growth hormone-deficient rats. 792 70

Recent results suggest that insulin-like growth factor-I (IGF-I) may be involved in the transition of a hemodynamic load into cardiac hypertrophy and that the expression of IGF-I seems to be coupled to increased wall stress. The present study investigated the role of growth hormone (GH) and IGF-I in myocardial hypertrophy induced by volume overload. An aortocaval fistula (ACF) was created in male Wistar rats, and experiments were performed 2, 4, and 7 days after the onset of volume overload. Right and left ventricular (RV and LV, respectively) myocardial expression of GH receptor mRNA and IGF-I mRNA were quantitated by a solution hybridization RNase protection assay. RV GH receptor mRNA content was elevated on the fourth and seventh days after the induction of the shunt, with peak levels (0.63 +/- 0.16 versus 0.14 +/- 0.03 amol/microgram DNA for the sham-operated animals; P < .01) after 4 days. Similarly, IGF-I mRNA was significantly increased in the RV of shunted animals (1.26 +/- 0.13 versus 0.56 +/- 0.05 amol/micrograms DNA; P < .01) 7 days after surgery. In the left ventricle, where systolic pressure was reduced in ACF rats, no differences could be detected in GH receptor and IGF-I mRNA content between ACF and sham-operated rats on any of the experimental days. There was no difference in the ratio of RV to LV weight during the experimental period. We have shown that the thin-walled right ventricle responds to volume overload with an increase of GH receptor mRNA content followed by elevated expression of IGF-I mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Jun
PMID:Increased expression of growth hormone receptor mRNA and insulin-like growth factor-I mRNA in volume-overloaded hearts. 820 22

Tyrosine kinases have been implicated in vascular smooth muscle cell proliferation and contraction. Underlying mechanisms may involve C(a2+) -dependent pathways. This study assesses relationships between angiotensin II (Ang II)-stimulated phospholipase C-mediated Ca2+ transients and tyrosine kinase-dependent pathways in vascular smooth muscle cells. Intracellular free Ca2+ concentration ([Ca2+]i) was measured in primary cultured unpassaged vascular smooth muscle cells derived from mesenteric resistance vessels of Wistar-Kyoto rats with the use of fura 2 methodology. [Ca2+]i effects of Ang II (1 nmol/L) were determined in vascular smooth muscle cells in which tyrosine kinase pathways were stimulated by insulin (70 muU/mL; 0.5 nmol/L), insulin-like growth factor-I (1 ng/mL; 0.13 nmol/L), or platelet-derived growth factor-BB (1 ng/mL; 0.04 nmol/L) and in cells in which tyrosine kinase was inhibited by specific inhibitors (1 mumol/L tyrphostin A-23 and genistein). Ang II elicited a rapid and transient [Ca2+]i response (from 94 +/- 8 to 239 +/- 5.8 nmol/L). Activation of the receptor tyrosine kinase by insulin, platelet-derived growth factor, and insulin-like growth factor-I significantly reduced (P < .01) Ang II-induced [Ca2+]i to 161 +/- 7, 189 +/- 3.7, and 183 +/- 5 nmol/L, respectively. In the presence of tyrphostin A-23 and genistein, Ang II-stimulated [Ca2+]i remained persistently elevated and failed to return to basal levels. Tyrphostin A-1, the inactive tyrphostin analogue, had not significant effect on Ang II-induced [Ca2+]i. This study demonstrates that activation of tyrosine kinase pathways reduces Ang II-elicited [Ca2+]i responses, whereas tyrosine kinase inhibition prevents [Ca2+]i recovery after agonist stimulation. Interaction between tyrosine kinase- and phospholipase C-dependent signaling pathways modulates vascular smooth muscle cell [Ca2+]i responses to Ang II.
Hypertension 1996 May
PMID:Tyrosine kinase signaling pathways modulate angiotensin II-induced calcium ([Ca2+]i) transients in vascular smooth muscle cells. 862 Dec 2

Induction of two-kidney, one clip hypertension (renal hypertension) is characterized by a slow increase in left ventricular tension and aortic wall stress, as opposed to aortocaval fistula or shunt volume overload, which induces a marked and rapid onset of wall stress in the caval vein and right ventricle. In the present study, we applied hemodynamic challenge to study the growth response involving gene expression of insulin-like growth factor-I (IGF-I) and growth hormone receptor (GH-R) mRNA in aorta and caval vein. Volume overload and pressure overload were induced in Wistar rats by means of shunt and renal hypertension, respectively. Systolic pressure was measured before excision of the great vessels, which was performed between 2 and 12 days postoperatively. Aortic and caval vein IGF-I and GH-R mRNA expressions were measured by means of a solution hybridization assay, and the caval vein was analyzed for IGF-I protein by immunohistochemistry. In the volume-distended but not pressurized caval vein in shunt rats, verified by telemetry recordings, there was an eightfold increase in IGF-I and 3.5-fold increase in GH-R mRNA at day 4 versus control. The IGF-I protein appeared to be localized in smooth muscle cells. In the aorta of the renal hypertension group, changes were of a slower onset. At day 7, there was a fourfold increase in IGF-I and five-fold increase of GH-R mRNA expressions versus sham-operated rats. Both the shunt caval vein and renal hypertension aorta showed evidence of a structural adaptation of the growth response. The present study suggests that acute elevation in vascular wall stress is an important triggering factor for overexpression of IGF-I and GH-R mRNA in great vessels. The growth hormone/insulin-like growth factor axis may be an important link in mediating structurally adaptive growth responses in the blood vessel wall.
Hypertension 1997 Jan
PMID:Induction of growth hormone receptor and insulin-like growth factor-I mRNA in aorta and caval vein during hemodynamic challenge. 903 91

A growing body of evidence indicates that the individual genetic background plays a role in the pathogenesis of diabetic glomerular disease by either favoring or protecting against injury produced by hyperglycemia. Two genetically related rat strains, the Milan normotensive strain (MNS) and the Milan hypertensive strain (MHS) display different susceptibilities to develop glomerulosclerosis with age. Glomerular sclerosing lesions occur in the MNS rats, which remain normotensive throughout their entire life-span, but not in the MHS rats, despite the presence of arterial hypertension. Previous studies have reported that extracellular matrix production and cell proliferation increased with donor-aging in mesangial cells isolated from MNS rats, but not in those from MHS rats, thus suggesting the existence of an inherited defect in the regulation of cell and matrix turnover, which translates into an abnormal response to growth-promoting stimuli favoring the development of glomerulosclerosis. In the study presented here, it was hypothesized that, in addition to donor-aging, other independent risk factors for the development of glomerular disease, such as metabolic injury by hyperglycemia, would be able to trigger and/or precipitate the occurrence of these changes in mesangial cells from the susceptible normotensive strain, but not in those from the protected hypertensive strain. To test this hypothesis, mesangial cells obtained from these rat strains (before the onset of either glomerulosclerosis or hypertension) were used to assess the effects of prolonged (4 wk) exposure to high (30 mmol/L) versus normal (5.5 mmol/L) glucose concentrations on extracellular matrix and cytokine production and cell proliferation. The accumulation and/or gene expression of the matrix components fibronectin, laminin, and collagen IV, and of the cytokines insulin-like growth factor-I (IGF-I) and transforming growth factor-beta (TGF-beta) did not change under normal glucose and increased progressively in response to high glucose in both MNS and MHS cells. These increases, with the exception of the increment in TGF-beta gene expression, were significantly more pronounced in MNS cells than in MHS cells. In contrast, the proliferative response to serum was not affected by high glucose, but increased in MNS cells, and decreased, although not significantly, in MHS cells during the 4-wk period, thus mimicking the changes previously observed in these rat strains as a function of age. These results indicate that high glucose unmasks a genetic tendency to produce increasing amounts of extracellular matrix, not yet evident under normal glucose conditions, and suggest that a genetically determined propensity of mesangial cells to hyperrespond to chronic hyperglycemia may be implicated in the pathogenesis of diabetic glomerular disease.
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PMID:High glucose level unmasks a genetic predisposition to enhanced extracellular matrix production in mesangial cells from the Milan normotensive strain. 907 9

We encountered a 91-year-old patient with acromegalic features. The serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) were increased to 23.3 ng/ml and to 268 ng/ml, respectively. Both thyrotropin-releasing hormone and luteinizing hormone-releasing hormone tests demonstrated a 2-3 fold increase in the serum GH level. Magnetic resonance imaging disclosed a pituitary mass in the enlarged sella. The patient was diagnosed as having acromegaly due to overproduction of GH from a pituitary tumor. She manifested cardiac hypertrophy with severe aortic stenosis and mild hypertension, but without diabetes mellitus. After the administration of octreotide subcutaneously at a dose of 25 to 50 micrograms daily for 20 days, the serum GH level increased transiently but decreased rapidly to approximately half the initial level, and suppression of the GH level persisted thereafter for over 2.5 months. This patient seems to be the oldest patient with acromegaly among those reported in Japan.
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PMID:A case report of an elderly patient with acromegaly. 907 12

We evaluated the protective effects of manidipine, which is a long-lasting calcium-channel blocker, against damage to spermatogenesis arising from hypertensive vascular changes in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP showed severe hypertension at 11 weeks of age, followed by hypertensive changes in intratesticular arterioles from 15 weeks of age. Manidipine lowered the blood pressure and the hypertensive vascular changes of intratesticular arterioles in SHRSP. The percentages of atrophic seminiferous tubules and tubules with less-differentiated germ cells were increased in SHRSP at 23 weeks of age, although the administration of manidipine preserved spermatogenesis at a normal level. The transferrin concentration in testicular cytosol was comparable, whereas insulin-like growth factor-I (IGF-I) was reduced from 19 weeks of age in SHRSP. Manidipine preserved the normal IGF-I concentration. Therefore, manidipine prevented the development of hypertensive vascular changes in the testis and maintained normal Sertoli cell function. As a result, manidipine protected spermatogenesis in SHRSP. These findings also suggested that hypertensive vascular changes in the testes play the most important role in spermatogenic damage in SHRSP.
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PMID:Manidipine improves spermatogenesis in the stroke-prone spontaneously hypertensive rat. 915 16

Insulin and insulin-like growth factor-I (IGF-I) may play a role in the modulation of coronary artery tone, yet there are few data regarding their vasoactive effects on the coronary vascular bed. We evaluated the vasorelaxation effects of insulin and IGF-I on porcine coronary epicardial vessels in vitro and elucidated possible mechanisms. Porcine epicardial arteries were contracted with 10(-7) mol/L endothelin-1 and relaxed with cumulative concentrations of either insulin or IGF-I (10(-12) to 10(-7) mol/L). The above experiments were repeated in vessels without endothelium. Vessels were also incubated with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 10(-4) mol/L) with and without 10(-3.5) mol/L L-arginine, the potassium channel blocker tetraethylammonium (TEA; 10(-2) mol/L), and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-alpha]quinoxalin-1-one (ODQ; 10(-5.5) mol/L); vessels were then contracted with endothelin-1 and relaxed with insulin or IGF-I. Insulin and IGF-I were also added after contraction with 60 mmol/L KCl. Insulin and IGF-I caused a similar decrease in coronary epicardial tension after contraction with endothelin-1 (relaxation of 28+/-4% [n=7] and 25+/-3% [n=8] with insulin and IGF-I, respectively; P<0.0001 for both peptides). Removal of the endothelium did not affect these responses. Incubation with L-NMMA, but not ODQ, attenuated the vasorelaxation response to insulin and IGF in vessels without endothelium. L-Arginine did not reverse this effect of L-NMMA. KCl and TEA attenuated the vasorelaxation effect of both insulin and IGF-I. Thus, both insulin and IGF-I caused non-endothelium-dependent coronary vasorelaxation in vitro, probably through a mechanism involving the activation of potassium channels. These findings suggest that insulin and IGF-I participate in the regulation of coronary vasomotor tone.
Hypertension 1998 Aug
PMID:Insulin and insulin-like growth factor-I cause coronary vasorelaxation in vitro. 971 47

Physical forces induce profound changes in cell phenotype, shape and behavior. These changes can occur in vascular structures as a result of pressure overload and their effects can be seen in atherosclerotic vessels in which smooth muscle cells have undergone hyperplastic and hypertrophic changes. At the molecular level, mechanical stimuli are converted into chemical ones and lead to modulation of gene expression and/or the activation of a new repertoire of genes whose encoded proteins help the cells to adapt to their microenvironment. In this study, we have used a two primer-based mRNA differential display technique to identify candidate mechano-responsive genes in pulmonary artery smooth muscle cells. As compared to the original method described by Liang and Pardee, this technique uses two arbitrary primers instead of an anchored oligo(dt) plus an arbitrary primer in the polymerase chain reaction. The chief advantages of these modifications are an increase in the efficiency of the amplification and in the identification of differentially expressed clones. Using this approach, we compared the pattern of expressed genes in cells cultured under static conditions with those in cells that were mechanically stretched (1 Hz) for 24 h in a well-defined in vitro mechanical system. Three candidate genes that showed reproducible differences were chosen for further characterization and cloning. One clone was under expressed in stretched cells and had a DNA sequence with 90% homology to the human fibronectin gene. Two other clones were highly expressed in stretched cells and had a 92% and a 83% sequence homology with human platelet-activating factor (PAF) receptor and rat insulin-like growth factor-I (IGF-I) genes respectively. Northern blot analysis confirmed low levels of fibronectin mRNA transcripts in stretched cells. In contrast, accumulation of PAF receptor mRNA occurred 30 min after mechanical stretch was initiated whereas IGF-I mRNA levels peaked at 8 h. Both mRNA levels were sustained for up to 24 h of mechanical stretching. These results demonstrate the usefulness of the two primer-based mRNA differential display that enabled us to identify and characterize alterations at the level of gene expression among matrix proteins, G-protein coupled receptors and growth factors, each of whose response to mechanical strain is different. A more complete understanding of these responses will provide further insight into the pathologic processes associated with hypertension and atherosclerosis.
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PMID:Identification of stretch-responsive genes in pulmonary artery smooth muscle cells by a two arbitrary primer-based mRNA differential display approach. 1048 28


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