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

Structural changes of the arteries in hypertension are determined by the unique genetics of the animals and by various growth promoters and growth inhibitors. Vascular smooth muscle cell growth promoting factors include fibroblast growth factor, platelet-derived growth factor, and vasoactive peptides such as norepinephrine, angiotensin II, and endothelin. Endothelial cells secrete three types of growth inhibiting factors. These are heparin--heparan sulfate, transforming growth factor beta, and nitric oxide. The effect of sympathetic innervation on vascular growth is probably dependent on its interaction with the renin-angiotensin system. In the mesenteric vascular bed, the elevated resistance in the arterial system is present in both the macroarteries and in the more distal microarteries and veins. Changes in resistance arteries include hypertrophy and reduction in outer diameter (remodelling). In the resistance arteries from human essential hypertensives, remodelling is the predominant finding. Long-term treatment with an angiotensin I converting enzyme inhibitor but not with a beta-blocker was effective in reversing this type of vascular change. Studies have suggested that in addition to angiotensin II, endothelin may play a role in vascular remodelling of resistance arteries.
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PMID:Pathophysiology of smooth muscle in hypertension. 758 23

Vascular smooth muscle cells (VSMC) are the principal cellular component of the blood vessel wall. Atherosclerosis, hypertension, and angiogenesis are associated with abnormal VSMC growth. Angiotensin II is hypertrophic for cultured adult rat aortic VSMC, whereas platelet-derived growth factor and serum are hyperplastic. To identify changes in specific proteins associated with either hyperplastic or hypertrophic growth, high resolution two-dimensional gel electrophoresis was performed on extracts from quiescent rat aortic VSMC and from VSMC exposed for 24 h to growth factors (10% fetal calf serum, platelet-derived growth factor, or angiotensin II). 12 proteins were up-regulated and 5 down-regulated by treatment with growth factors. Eight of the up-regulated and one of the down-regulated proteins were identified by internal protein microsequencing from electroblotted two-dimensional gels or by co-electrophoresis of purified proteins in two-dimensional gels. Four of the proteins up-regulated by growth factors were identified as mediators of protein folding. These were heat shock proteins, HSP-60 and HSP-70, protein disulfide isomerase, and protein disulfide isomerase isozyme Q-2. Additional proteins were identified as elongation factor EF-1 beta, a component of the protein synthesis apparatus, and calreticulin, another putative molecular chaperone. Vimentin and actin were also up-regulated, whereas an isoform of myosin heavy chain was down-regulated. Hyperplastic and hypertrophic growth were accompanied by similar changes in protein expression, suggesting that both types of growth require up-regulation of the protein synthesis and folding machinery.
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PMID:Components of the protein synthesis and folding machinery are induced in vascular smooth muscle cells by hypertrophic and hyperplastic agents. Identification by comparative protein phenotyping and microsequencing. 767 76

Several experimental studies point to a potential role of angiotensin II (Ang II) in the progression of glomerulosclerosis even in the absence of glomerular hypertension. We tested the hypothesis that Ang II acts as a growth factor for adult human mesangial cells (AHMC). AHMC were isolated from noninvolved parts of tumor nephrectomy specimens and grown in RPMI medium with the addition of fetal calf serum (FCS). All studies were performed with growth-arrested cells. Proliferation studies were done in serum-free standard growth medium (SF) with the addition of either various concentrations of insulin, plasma-derived serum, or FCS. Ang II (10(-10) to 10(-6) M) dose dependently increased the 3H-thymidine uptake of AHMC up to 57 +/- 13% over solvent controls (p < 0.01). In parallel, the DNA content was 36 +/- 10% higher (p < 0.05) than in solvent controls after 2 days of culture. The cell numbers were higher up to 47 +/- 8% in Ang II (10(-6) M) stimulated cultures after 4 days of incubation (p < 0.01). The effect of Ang II was specific, since it was almost completely obliterated by the AT1 receptor antagonist DuP753. The effect of Ang II was particularly marked when cultures were incubated with SF plus high concentrations (1.7 x 10(-6) M) of insulin or SF plus 10% plasma-derived serum. In contrast, the effect was not significant when cultures were incubated with SF plus 10% FCS. Ang II, when added to platelet-derived growth factor at various concentrations, did not further increase the proliferation. The effect on protein synthesis was assessed in growth-arrested AHMC by 3H-methionine uptake and protein/DNA ratio in cell lysates. Ang II (10(-10) to 10(-6) M) dose dependently increased the 3H-methionine uptake of AHMC up to 47 +/- 10% over solvent controls (p < 0.01). In parallel Ang II (10(-8) to 10(-6) M) dose dependently increased the 3H-methionine uptake of the protein/DNA ratio by 24 +/- 6% after 48 h of incubation. DuP753 obliterated the stimulatory effect of Ang II. Ang II (10(-6) M) also increased the mRNA of the immediate-early growth-related gene Egr-1. We conclude that Ang II induces hypertrophy and proliferation in adult human mesangial cells. This result is of interest with respect to a potential role of Ang II in the pathogenesis of glomerulosclerosis in humans.
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PMID:Angiotensin II induces hypertrophy and hyperplasia in adult human mesangial cells. 771 40

Adrenomedullin recently has been found to potently stimulate cAMP formation in cultured rat vascular smooth muscle cells (VSMCs). In the present study, we examined the effect of adrenomedullin on the production of a vasoconstrictive and growth-promoting peptide, endothelin-1, after stimulation with a clotting enzyme, thrombin, and a potent mitogen, platelet-derived growth factor (PDGF), in cultured rat VSMCs. Thrombin and PDGF stimulated endothelin-1 production in a dose-dependent manner. Rat adrenomedullin significantly inhibited thrombin- and PDGF-stimulated endothelin-1 production in a dose-dependent manner between 10(-7) and 10(-9) mol/L. Inhibition by rat adrenomedullin of thrombin- and PDGF-stimulated endothelin-1 production was paralleled by an increase in the cellular level of cAMP. Human adrenomedullin also inhibited thrombin- and PDGF-stimulated endothelin-1 production and increased cAMP levels. The addition of 8-bromo-cAMP, a cAMP analogue, reduced thrombin- and PDGF-induced endothelin-1 production. Furthermore, forskolin, a potent activator of adenylate cyclase, reduced thrombin- and PDGF-induced endothelin-1 production. In contrast, basal production of endothelin-1 was not altered by rat or human adrenomedullin. These results indicate that adrenomedullin inhibits not basal but thrombin- and PDGF-induced ET-1 production in cultured VSMCs probably through a cAMP-dependent process. Taken together with the finding that adrenomedullin is synthesized in and secreted from vascular endothelial cells, adrenomedullin may modulate vascular tone as a paracrine regulator partially through the inhibition of VSMC endothelin-1 production in some pathophysiological states.
Hypertension 1995 Jun
PMID:Inhibition of endothelin production by adrenomedullin in vascular smooth muscle cells. 776 61

Mesangial cells possess Ca(2+)-activated Cl- channels, Ca(2+)-activated K+ channels, voltage-gated Ca2+ channels, ATP-sensitive K+ channels, and two types of nonselective cation channels. Angiotensin II and arginine vasopressin depolarize the membrane. This membrane depolarization is caused by the activation of Ca(2+)-activated Cl- and Ca(2+)-activated nonselective cation channels through an elevation of intracellular Ca2+ concentration. The Ca(2+)-independent nonselective cation channel is activated by platelet-derived growth factor and is a candidate for the receptor-activated Ca2+ influx system. It has been suggested that macula densa Cl- reabsorption determines the Cl- concentration of juxtaglomerular apparatus interstitial fluid and thereby affects the resistance of afferent arterioles. In addition, angiotensin II-mediated and arginine vasopressin-mediated mesangial cell Ca2+ signals and contraction are attenuated via prostaglandin production by the mesangial cells themselves when the ambient Cl- concentration is reduced. Thus, Cl- plays an essential role in the tubuloglomerular feedback mechanism. The intracellular Ca2+ concentration appears to be important for the signal transduction mechanism of tubuloglomerular feedback. The ionic channels on the mesangial cell membrane may participate in controlling the intracellular Ca2+ concentration. The association of disturbed tubuloglomerular feedback and the development of hypertension has recently been reported.
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PMID:Mesangial cell ion transport and tubuloglomerular feedback. 780 50

Structural changes of the heart and blood vessels participate in the long-term regulation of the cardiovascular system. In hypertension and myocardial dysfunction, the adaptive process of cardiac and vascular remodeling may contribute to the pathophysiology and complications of these diseases. Recent investigations have enhanced our understanding of the cellular and molecular biology of vascular smooth muscle and cardiac myocyte growth. Mechanical and neurohormonal factors can independently stimulate hypertrophy-hyperplasia in vascular and cardiac myocytes. Increased pressure-stretch of cardiac myocyte and vascular smooth muscle cells can activate protooncogene expressions that may mediate the growth response. Vasoactive substances also regulate cardiovascular growth. In general, endogenous vasoconstrictors (eg, angiotensin, endothelin) act as growth promoters, and endogenous vasodilators (eg, nitric oxide, prostacyclin, atrial natriuretic peptide) act as growth inhibitors of vascular smooth muscle and, possibly, cardiac myocytes. Recent data have demonstrated that the vasoconstrictive agents, such as angiotensin, activate protooncogenes and autocrine growth factors that mediate vascular growth. Furthermore, the development of vascular hypertrophy versus hyperplasia is dependent on the relative activation of endogenous proliferative growth factor (eg, platelet-derived growth factor, basic fibroblast growth factor) versus antiproliferative factor (eg, transforming growth factor-beta) by the growth stimulus. Taken together, these data demonstrate that complex interactions of local mediators, which participate in the pathophysiology of cardiovascular diseases, control cardiovascular growth.
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PMID:The role of mechanical and humoral factors in growth regulation of vascular smooth muscle and cardiac myocytes. 792 63

1. Platelet volume was measured in citrated blood in two groups of patients at risk of having atherosclerotic renal artery stenosis, namely (i) 30 patients with severe hypertension, and (ii) 44 patients with peripheral vascular disease. 2. Platelet volume was increased in patients with hypertension who had atherosclerotic renal artery stenosis diagnosed by angiography: no renal artery stenosis, median 7.2 (interquartile range 0.5) x 10(-15)/l; renal artery stenosis 7.8 (0.8) x 10(-15)/l; platelet mass also increased with increasing severity of renal artery stenosis. Platelet volume correlated with severity of renal artery stenosis (rs = 0.391, 2p = 0.033, n = 30). Similarly, platelet volume correlated with severity of renal artery stenosis in patients with peripheral vascular disease (rs = 0.319, 2p = 0.035, n = 44). Serum immunoreactive platelet-derived growth factor (predominantly released from platelets) and plasma immunoreactive interleukin-6 (a cytokine which has been postulated to regulate platelet volume) concentrations were not different between hypertensive patients with and without renal artery stenosis. 3. Since large platelets are hyperactive, increased platelet volume may contribute to the development of atherosclerotic renal artery stenosis. However, the present data do not lend support to the hypothesis that platelet-derived growth factor is central to renal artery atherogenesis. Interleukin-6 does not appear to regulate platelet volume.
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PMID:Increased platelet volume and platelet mass in patients with atherosclerotic renal artery stenosis. 792 72

The main target organ in untreated arterial hypertension (HTA) is the blood vessel wall (BVW) of the high pressure system (conductance and resistance arteries), which is primarily responsible for vital organ integrity. Three major structural changes develop in the BVW in experimental and human HTA: hypertrophy of the smooth muscle (increased thickness of the media), reduction in the amount of elastin and increased interstitial collagen deposition. The latter two structural changes are responsible for the increased stiffness (reduced compliance) that characterizes the BVW in untreated HTA. Angiotensin II, endothelins, nitric oxide, local growth factors (fibroblast-derived growth factor, platelet-derived growth factor, transforming growth factor-beta) and metalloproteinases are involved in BVW remodelling, and represent potential targets for drug action. Angiotensin-converting enzyme (ACE) inhibitors are particularly suited for such actions via their angiotensin II-, bradykinin- and/or interstitial metalloproteinases-dependent actions. Unfortunately, limited data are available on BVW protection with conventional ACE inhibitors. The new ACE inhibitor perindopril differs from most others in terms of BVW protection. In carefully designed morphometric experiments, perindopril has been shown to reduce vascular smooth muscle hypertrophy and to normalize the elastin:collagen ratio in the BVW of hypertensive rats. It has been shown that perindopril is unique in that respect since isradipine, metoprolol, hydralazine and captopril all failed to normalize the media:lumen ratio in the hypertensive rat. The functional counterpart of these in vitro structural findings obtained with perindopril has been demonstrated in human HTA patients; increased brachial artery diameter and compliance were observed after three weeks of perindopril.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The blood vessel as a target organ in hypertension: protective effect of perindopril. 795 36

The mechanisms of vascular structural alterations in hypertension were studied in cultured adventitial fibroblasts isolated from aortas of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Basic fibroblast growth factor (bFGF)-, epidermal growth factor (EGF)-, or platelet-derived growth factor (PDGF)-induced DNA synthesis and phospholipase C activity were estimated by determining 3H-thymidine incorporation and 3H-inositol phosphate production, respectively. The role of protein tyrosine kinases was assessed by stimulating the cells in the presence of tyrphostin, a protein tyrosine kinase inhibitor. Both the mitogenic potency of bFGF, EGF, and PDGF and the phospholipase C activity elicited by these factors were increased markedly in SHR (v WKY) fibroblasts. SHR fibroblasts were significantly less sensitive to tyrphostin inhibition of bFGF-induced 3H-thymidine incorporation than WKY fibroblasts, whereas when the cells were stimulated with EGF, PDGF, or 5% serum, SHR and WKY fibroblasts were equally sensitive to tyrphostin inhibition. At doses that abolished bFGF-induced 3H-thymidine incorporation, tyrphostin did not affect bFGF-induced 3H-inositol phosphate production. These results indicate that in aortic fibroblasts phospholipase C activation is not sufficient for bFGF-induced DNA synthesis. They suggest that tyrosine kinase activation is a necessary step in the transduction of bFGF mitogenic signal and plays an important role in the enhanced DNA synthesis exhibited by SHR (v WKY) cells. Therefore, one may envisage that bFGF contributes, through paracrine/autocrine mechanisms, to the vascular smooth muscle hyperplasia/hypertrophy in SHR.
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PMID:Signaling mechanisms of basic fibroblast growth factor in arterial cells from genetically hypertensive rat. 803 51

Effects of two major potent vasoconstrictors, angiotensin II and platelet-derived growth factor, on elastin expression in cultured chick embryonic arterial smooth muscle cells were studied. Platelet-derived growth factor exhibited no effect on elastin synthesis nor its mRNA level but stimulated (1.5-fold) cell proliferation slightly. Angiotensin II inhibited elastin synthesis dose- and time-dependent manner with a maximum suppression of sixty percent of control at a concentration of 10 microM for 18 h treatment. The suppression was accompanied with a comparable decrease in elastin mRNA level. The inhibition was blocked by addition of Sar1,Ala8-angiotensin II and 8-bromo-cGMP. It showed no effect on cell proliferation. Angiotensin II appears to inhibit elastin synthesis through the interaction with its receptor and the modulation of intracellular Ca2+ level. Thus angiotensin II, not platelet-derived growth factor, can exert a profound effect on the extracellular matrix composition in arterial walls, leading to an arterial change in hypertension or atherosclerosis.
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PMID:Elastin synthesis is inhibited by angiotensin II but not by platelet-derived growth factor in arterial smooth muscle cells. 804 11


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