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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous investigations have demonstrated certain similarities in the cellular changes occurring in the arterial wall in response to hypertension and aging. We undertook the current studies to examine the expression of platelet-derived growth factor (PDGF) receptors and ligands and transforming growth factor-beta 1 (TGF-beta 1) in aorta and heart of spontaneously hypertensive rats (SHRs), Wistar-Kyoto (WKY) controls, and Wistar rats studied at ages ranging from 5 to 40 weeks. A progressive increase with age in aortic steady-state messenger RNA (mRNA) levels of the receptor for the B chain of PDGF (PDGF-r beta) was present in all three strains but was greatest in the SHR. The aortic expression of PDGF A or B ligands as well as of the PDGF-r alpha-receptor was not significantly influenced by age or blood pressure. In contrast, in the heart of the SHR and WKY rat, there was an age-related decrease in expression of both PDGF receptors and of the PDGF B chain. Hypertension and aging were associated with increases in steady-state mRNA for TGF-beta 1 in aorta, but in the heart, reductions again were observed. These studies indicate that both hypertension and aging increase the in vivo expression of PDGF-r beta and TGF-beta 1 in aortic tissue. Such changes might be functionally significant and provide autocrine or paracrine mechanisms for regulation of cellular growth in the arterial wall in response to these conditions. The findings also provide further support for the concept that hypertension accelerates the arterial changes associated with aging.
Hypertension 1991 Nov
PMID:Effects of hypertension and aging on platelet-derived growth factor and platelet-derived growth factor receptor expression in rat aorta and heart. 165 76

In cultured vascular smooth muscle cells, the baseline mRNA and protein levels of an inducible type of nitric oxide synthase were barely detectable. Interferon gamma, tumor necrosis factor-alpha, and interleukin-1 beta each markedly increased mRNA and protein levels of this enzyme in parallel with the production of nitrite, a stable oxidative metabolite of nitric oxide. Actinomycin D abolished the cytokine-induced increases in mRNA levels and nitrite production. Cycloheximide, which abolished the cytokine-induced increase in nitrite production, had no effect on the interferon-gamma-induced increase in mRNA levels but partially inhibited that induced by interleukin-1 beta and markedly inhibited that induced by tumor necrosis factor-alpha. Transforming growth factor-beta 1, which inhibited the interferon gamma-, interleukin-1 beta-, and tumor necrosis factor-alpha-induced nitrite production, did not affect the increases in mRNA levels caused by these cytokines. Transforming growth factor-beta 1, however, significantly inhibited the increase in protein levels caused by these cytokines. These findings suggest that interferon gamma directly induces the expression of the inducible nitric oxide synthase gene, whereas tumor necrosis factor-alpha and interleukin-1 beta induce it, at least in part, via the induction of intermediary protein(s), and that transforming growth factor-beta 1 inhibits cytokine-induced nitric oxide production by blocking the posttranscriptional synthesis of inducible nitric oxide synthase.
Hypertension 1994 Jan
PMID:Expression of nitric oxide synthase by cytokines in vascular smooth muscle cells. 750

We have previously reported that renal mRNA levels for transforming growth factor-beta 1, fibronectin, and collagens were increased in 32-week-old stroke-prone spontaneously hypertensive rats (SHRSP) with severe nephrosclerosis. To elucidate the mechanism of hypertension-induced nephrosclerosis, we examined gene expression and localization of transforming growth factor-beta 1 and cellular phenotype in the kidney of 25-week-old SHRSP with moderate renal damage. Renal mRNA was measured by Northern blot analysis. The localization of transforming growth factor-beta 1 and cellular phenotype was determined by immunohistochemistry. In the kidney of 25-week-old SHRSP, renal transforming growth factor-beta 1 mRNA was elevated compared with Wistar-Kyoto rats (WKY), whereas renal collagen mRNAs of SHRSP were not increased. Immunoreactive transforming growth factor-beta 1 in SHRSP was mainly localized in glomerular cells. Furthermore, alpha-smooth muscle actin and desmin were significantly expressed in SHRSP glomerular cells, in contrast to negligible expression of these proteins in WKY. alpha-Smooth muscle actin staining was also observed in interstitial cells, and vimentin, another phenotypic marker, was expressed in atrophic tubular cells of SHRSP, despite no staining of these proteins in WKY. Furthermore, all these phenotypic changes in SHRSP were associated with increased cell proliferation, as shown by the increased number of proliferating cell nuclear antigen-positive cells. Treatment of SHRSP with cilazapril and nifedipine (from the age of 13 to 25 weeks) prevented the increase in transforming growth factor-beta 1 expression and the cellular phenotypic modulation and was accompanied by a reduction of urinary albumin excretion and inhibition of cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Jul
PMID:Transforming growth factor-beta 1 expression and phenotypic modulation in the kidney of hypertensive rats. 754 81

To clarify whether the growth inhibitors, transforming growth factor-beta 1 (TGF-beta 1), heparin, and interferon-gamma (IFN-gamma) contribute to the development of vascular hypertrophy in spontaneously hypertensive rats (SHR), the growth of vascular smooth muscle cells (VSMC) was evaluated both for cell numbers over a period of 4 days, and [3H]thymidine incorporation over 24 h. Heparin and IFN-gamma inhibited the proliferation of VSMC from SHR and Wistar-Kyoto (WKY) rats. TGF-beta 1 enhanced SHR-VSMC proliferation by 16.6 +/- 8.9%; in contrast TGF-beta 1 inhibited WKY-VSMC proliferation by 60.5 +/- 7.4%. There was no difference in affinity, number of binding sites, or subtype expression of TGF-beta 1 receptor between SHR-VSMC and WKY-VSMC. This evidence suggests that the signal transduction system of TGF-beta 1 either the receptor itself or downstream signaling molecules, may be altered in SHR-VSMC versus WKY-VSMC. This abnormal responsiveness to TGF-beta 1 is involved in the proliferative characteristics of SHR-VSMC. Therefore, TGF-beta 1 could contribute to the development of hypertension or vascular hypertrophy in SHR.
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PMID:Transforming growth factor-beta 1 proliferated vascular smooth muscle cells from spontaneously hypertensive rats. 775 44

Cardiac phenotypic modulation and remodeling appear to be involved in the pathophysiology of cardiac hypertrophy and heart failure. We undertook this study to examine whether angiotensin II (Ang II) in vivo, independent of blood pressure, contributes to cardiac phenotypic modulation and remodeling. A low dose (200 ng/kg per minute) of Ang II was continuously infused into rats by osmotic minipump for 24 hours or 3 or 7 days to examine the effects on the expression of cardiac phenotype-related or fibrosis-related genes. This Ang II dose caused a small and gradual increase in blood pressure over 7 days. Left ventricular mRNAs for skeletal alpha-actin, beta-myosin heavy chain, atrial natriuretic polypeptide, and fibronectin were already increased by 6.9-, 1.8-, 4.8-, and 1.5-fold, respectively, after 24 hours of Ang II infusion and by 6.9-, 3.3-, 7.5-, and 2.5-fold, respectively, after 3 days, whereas ventricular alpha-myosin heavy chain and smooth muscle alpha-actin mRNAs were not significantly altered by Ang II infusion. Ventricular transforming growth factor-beta 1 and types I and III collagen mRNA levels did not increase at 24 hours and began to increase by 1.4-, 2.8-, and 2.1-fold, respectively, at 3 days. An increase in left ventricular weight occurred 3 days after Ang II infusion. Treatment with TCV-116 (3 mg/kg per day), a nonpeptide selective angiotensin type 1 receptor antagonist, completely inhibited the above-mentioned Ang II-induced increases in ventricular gene expressions and weight. Hydralazine (10 mg/kg per day), which completely normalized blood pressure, did not block cardiac hypertrophy or increased cardiac gene expressions by Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Jun
PMID:Angiotensin II induces cardiac phenotypic modulation and remodeling in vivo in rats. 776 70

Recent evidence indicates that transforming growth factor-beta 1 (TGF-beta 1) plays an important role in renal fibrosis via stimulation of extracellular matrix synthesis. The present study was undertaken to investigate the role of angiotensin II type I receptor (AT1 receptor) in hypertension-induced renal injury. Twenty-two-week-old stroke-prone spontaneously hypertensive rats (SHRSP), which had established hypertension and moderate renal damage, were orally given TCV-116, a selective non-peptide AT1 receptor antagonist (0.1, 1 or 10 mg/kg/day), enalapril (10 mg/kg/day) or vehicle once a day for 10 weeks. At the end point of the treatment, we examined renal function, the gene expressions of TGF-beta 1 and extracellular matrix components in the interstitium [collagen types I (COI) and III (COIII), fibronectin (FN)] and the basement membrane (COIV and laminin), and renal microscopic morphology in rats aged 32 weeks. In vehicle-treated 32 week-old SHRSP with renal dysfunction and nephrosclerosis, renal mRNA levels for TGF-beta 1, COI, COIII, FN, COIV were all several-fold higher than in WKY. Thus, renal TGF-beta 1 gene expression was enhanced in SHRSP, which may contribute to the increased renal expressions of COI, COIII, FN, COIV in SHRSP. Treatment with TCV-116 (0.1 mg/kg/day) in SHRSP, in spite of no reduction of blood pressure, decreased renal mRNA levels for TGF-beta 1, COI, COIII, FN, COIV, being accompanied by the significant decrease in urinary protein and albumin excretion, blood urea nitrogen and plasma creatinine. Treatment with TCV-116 (10 mg/kg/day) in SHRSP decreased mRNAs for TGF-beta 1, COI, COIII, FN and COIV to almost the same levels as WKY, being associated with normalization of urinary protein and albumin excretion and the prevention of nephrosclerosis, as judged by microscopic histological observations. On the other hand, the effects of enalapril (10 mg/kg/day) on the above mentioned mRNA levels, renal function and renal morphology were weaker than those of TCV-116 (10 mg/kg/day) and were as much as TCV-116 (1 mg/kg/day). These results suggest that independently of hypotensive action, AT1 receptor antagonist has a potent renal protective effect by inhibiting the gene expression of renal TGF-beta 1 and extracellular matrix components.
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PMID:Contribution of renal angiotensin II type I receptor to gene expressions in hypertension-induced renal injury. 785 93

Two types of natriuretic peptide receptors (NPR-A and NPR-B) are membrane guanylate cyclases whose relative expression varies in different tissues. Because natriuretic peptides have been shown to inhibit aortic smooth muscle proliferation, we investigated the regulation of NPR-A and NPR-B in these cells under different proliferative conditions. NPR subtype mRNA levels were measured by our newly developed quantitative reverse transcription-polymerase chain reaction assay using mutated NPR-A and NPR-B cRNA as internal standards. The functional impact of their expression was determined by atrial natriuretic peptide (ANP)- and C-type natriuretic peptide (CNP)-induced stimulation of cyclic GMP production. In the intact aorta, NPR-B mRNA levels were found to be 10-fold higher than those of NPR-A. This dominance was further amplified (1000-fold) in long-term cultures (10 to 15 passages) of aortic smooth muscle cells (ASMC). Higher cyclic GMP production with CNP than with ANP was observed in cultured ASMC from Wistar-Kyoto (WKY) rats. Similar stimulation by the two agonists was noted in spontaneously hypertensive rat (SHR) cells, paralleled by a 10-fold increase in NPR-A mRNA levels and ANP stimulation of cyclic GMP in hypertensive cells. The present study also evaluated NPR-A and NPR-B mRNA control by transforming growth factor-beta 1 (TGF-beta 1), an important regulator of cell proliferation that is overexpressed in SHR ASMC. TGF-beta 1 decreased both NPR-A and NPR-B mRNA levels with a predominant effect in SHR cells at high cell density.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Jun
PMID:Regulation of natriuretic peptide receptor A and B expression by transforming growth factor-beta 1 in cultured aortic smooth muscle cells. 791 51

To investigate the role of angiotensin II (Ang II) in hypertension-induced tissue injury, we gave TCV-116 (1 mg/kg per day PO), a nonpeptide Ang II type I receptor antagonist, or enalapril (10 mg/kg per day PO) to deoxycorticosterone acetate (DOCA)-salt hypertensive rats for 3 weeks and examined the effects on tissue mRNA levels for transforming growth factor-beta 1 (TGF-beta 1) and extracellular matrix components. Tissue mRNA levels were measured by Northern blot analysis. Renal mRNA levels for TGF-beta 1; types I, III, and IV collagen; and fibronectin in DOCA-salt hypertensive rats were increased by severalfold (P < .01) compared with sham-operated rats. In the aorta of DOCA-salt hypertensive rats, TGF-beta 1 and fibronectin mRNA levels were increased, but types I, III, and IV collagen mRNAs did not increase. In the heart, increased mRNA was found only for fibronectin. Thus, these gene expressions are regulated in a tissue-specific manner. TCV-116 or enalapril did not lower blood pressure in DOCA-salt hypertensive rats. However, the increase in renal mRNAs for TGF-beta 1 and extracellular matrix components in DOCA-salt hypertensive rats was significantly inhibited by treatment with TCV-116 or enalapril, which was associated with a significant decrease in urinary protein and albumin excretions and histological improvement of renal lesions. In contrast, in the aorta and heart these gene expressions were not affected by TCV-116 or enalapril. Thus, local Ang II may contribute to renal injury of DOCA-salt hypertension by stimulating the gene expression of TGF-beta 1 and extracellular matrix components.
Hypertension 1994 Aug
PMID:Role of angiotensin II in renal injury of deoxycorticosterone acetate-salt hypertensive rats. 803 44

The role of angiotensin II via the angiotensin type 1 or type 2 receptor in the development of cardiac hypertrophy was determined in adult male Sprague-Dawley rats subjected to coarctation of the abdominal aorta. Five groups of animals were studied: coarctation, coarctation plus DuP 753, coarctation plus PD 123319, sham plus DuP 753, or sham operation. Type 1 receptor blockade was accomplished with DuP 753 given in the drinking water and type 2 blockade with PD 123319 delivered by osmotic minipumps beginning with the day of surgery until 72 hours after aortic coarctation. Mean carotid blood pressures and the carotid-femoral artery blood pressure gradients were not different among coarctation, coarctation plus DuP 753, and coarctation plus PD 123319 animals. However, ratios of heart weight to body weight were higher in coarctation (4.95 +/- 0.8) or coarctation plus PD 123319 (4.52 +/- 0.5) than in sham animals (3.6 +/- 0.4; P < .005 and .05, respectively). In coarctation plus DuP 753-treated animals heart weight-body weight ratios were not different from sham or sham plus DuP 753 animals (3.9 +/- 0.4 versus 3.6 +/- 0.4 or 3.3 +/- 0.08, respectively). Type 1 receptor mRNA levels were significantly increased in the coarctation group, with the highest levels in the coarctation plus DuP 753 and sham plus DuP 753 groups. To determine whether growth factors were involved in the hypertrophic process, we measured transforming growth factor-beta 1 mRNA levels. Northern analysis demonstrated a twofold increase in coarctation animals compared with sham or coarctation plus DuP 753-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 May
PMID:Angiotensin receptor regulates cardiac hypertrophy and transforming growth factor-beta 1 expression. 817 66

Cultured vascular smooth muscle cells derived from the spontaneously hypertensive rat (SHR) are known to replicate more rapidly than cells from the normotensive Wistar-Kyoto (WKY) rat. In this study we compared the responses of vascular smooth muscle cells from the two strains to transforming growth factor-beta 1 (TGF-beta 1) and evaluated its potential to account for the different growth properties of these cells in response to a number of vascular-derived growth factors. TGF-beta 1 potentiated the proliferative effects of epidermal growth factor, basic fibroblast growth factor, or the different isoforms of platelet-derived growth factor on vascular smooth muscle cells from SHR but inhibited growth factor-stimulated proliferation of vascular smooth muscle cells from WKY rats. These differential effects of TGF-beta 1 on proliferation could not be attributed to alterations in the expression of the type I, II, or III TGF-beta receptors but appeared more related to the ability of cells to autoinduce the TGF-beta 1 gene. TGF-beta 1 caused a time-dependent increase in its own mRNA levels in vascular smooth muscle cells of WKY rats but attenuated levels in vascular smooth muscle cells of SHR. This effect was specific to TGF-beta 1 autoinduction since similar elevations in TGF-beta 1 mRNA levels were observed when vascular smooth muscle cells from the two rat strains were exposed to phorbol myristate acetate, basic fibroblast growth factor, or platelet-derived growth factor-BB.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 May
PMID:Transforming growth factor-beta 1 gene activation and growth of smooth muscle from hypertensive rats. 817 67


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