摘要:

Cardiac hypertrophy is frequent in chronic hypertension. The renin-angiotensin system, via its effector angiotensin II (Ang II), regulates blood pressure and participates in sustaining hypertension. In addition, a growing body of evidence indicates that Ang II acts also as a growth factor. However, it is still a matter of debate whether the trophic effect of Ang II can trigger cardiac hypertrophy in the absence of elevated blood pressure. To address this question, transgenic mice overexpressing the rat angiotensinogen gene, specifically in the heart, were generated to increase the local activity of the renin-angiotensin system and therefore Ang II production. These mice develop myocardial hypertrophy without signs of fibrosis independently from the presence of hypertension, demonstrating that local Ang II production is important in mediating the hypertrophic response in vivo. (Hypertension. 1998;31:1324-1330.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The purpose of this investigation was to evaluate the role of blood pressure in the proliferative response of vascular smooth muscle cells to systemic infusion of angiotensin II (Ang II). Our laboratory has previously shown that infusion of Ang II induces smooth muscle cell proliferation in rat mesenteric vessels and carotid arteries. Ang II, a strong vasopressor, raised systolic blood pressure in rats from 120 to 200 mm Hg at a dose of 435 ng [center dot] kg-1[center dot] min-1after 1 week of treatment. The question arises as to whether this development of hypertension is a primary contributor to the replicative activities observed in the arterial wall of the mesenteric arteries or the carotid arteries or whether Ang II alone, without an increase in blood pressure, is sufficient to stimulate proliferation in these vessels. In the previous studies, we found that Ang II stimulated smooth muscle cell replication in the carotid artery and in type III and type I mesenteric microvessels. This study demonstrates that although administration of hydralazine normalizes the animals' blood pressures, it does not suppress the mitogenic effect of Ang II. Thus, it appears that Ang II has a direct effect on cell proliferation. (Hypertension. 1998;31:1331-1337.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We showed previously that liganded vitamin D receptor (VDR) effects a suppression of human atrial natriuretic peptide (hANP) gene-promoter activity in cultured neonatal rat atrial myocytes. In the present study, we have attempted to identify the structural domains of the VDR that are involved in mediating this suppression. We examined the effects of a series of VDR mutants on a cotransfected hANP promoter-driven chloramphenicol acetyltransferase (CAT) reporter. Neither the native VDR nor any of the mutants tested displayed inhibitory activity in the absence of the 1,25-dihydroxyvitamin D3(VD3) ligand. Delta 134, a deletant harboring solely the DNA binding region of the VDR, and L254G, a mutant shown to be defective in retinoid X receptor (RXR) heterodimer formation in other systems, were as effective as the native VDR in reducing promoter activity. HBD, a deletant containing only the hormone-binding domain of the VDR, and K246G, a point mutant that is defective in the activation function of the receptor, did not attenuate reporter activity. A similar activity profile was displayed when a positively regulated promoter containing a direct-repeat vitamin D responsive element (DR3-CAT) was examined in these cells. Liganded VDR, the Delta 134 mutant, and liganded L254G effected increases in DR3-CAT activity of 2.5-, 2-, and 4-fold, respectively. Two nonhypercalcemic analogues of VD3(RO 23-7553 and RO 25-6760) displayed the same inhibitory activity as VD3. These studies suggest that the inhibition of hANP promoter activity requires both the DNA binding and activation functions of the receptor but does not appear to require formation of a classic RXR alpha-VDR heterodimer. (Hypertension. 1998;31:1338-1342.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The purpose of the present study was to evaluate the effect of plasma from eclamptic and preeclamptic patients on cultured sympathetic nerve. Sympathetic neurons from 12- to 14-day-old chick embryos were cultured; the neurons were then stimulated with 50% plasma from eclamptic, preeclamptic, hypertensive, normotensive pregnant, hypertensive, and normotensive nonpregnant women (n=7). Similarly, neurons were individually incubated with mixtures of 50% corresponding plasma with 0.25% bupivacaine or bupivacaine only (n=7). Furthermore, the effects of 1%, 10%, and 50% plasma from eclamptic, preeclamptic, and normotensive pregnant patients (n=7) were also evaluated. Norepinephrine concentrations were measured by high-performance liquid chromatography. Electron microscopic studies of nerve cells were also performed. Stimulation with plasma from eclamptic and preeclamptic women significantly increased norepinephrine concentration (P<0.0001) compared with control. The release of norepinephrine was found to be concentration-dependent. Conversely, norepinephrine secretion was significantly hampered by bupivacaine treatment (P<0.0001). Electron microscopic studies in eclamptic and preeclamptic plasma-stimulated nerve cells showed that perikarya were in close contact with each other and with nerve cell processes. After treatment with bupivacaine, nerve cells were irregular in shape and the cell membranes were demyelinated. These results suggest that eclamptic and preeclamptic plasma has an excitotoxic effect on sympathetic nerve via axoplasmic membrane depolarization, thus increasing norepinephrine secretion that is blocked by bupivacaine. A preeclamptic condition may be improved by depression of sympathetic nerve stimulation. (Hypertension. 1998;31:1343-1349.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Septic shock involves systemic vasodilation mediated by proinflammatory cytokines. In essential hypertension, vascular and immune dysfunctions are closely associated. The response of hypertensive animals compared with normotensive controls to endotoxin (lipopolysaccharide; LPS) challenge is not known. Age-matched (12 weeks) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were exposed to intravenous injection of 10 mg/kg LPS. Survival rate at 24 hours was markedly higher in SHR than in WKY (12 of 15 and 3 of 15, respectively; P<0.01). Survival of LPS-injected SHR was not related to their hypertension because hydralazine-treated SHR with normalized pressure had similar survival rates, and WKY made hypertensive by clipping of one renal artery showed fatality similar to that of normotensive WKY. Continuous arterial pressure and sequential plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured in LPS-treated SHR and WKY. Both the duration of the delayed hypotensive phase and the systemic release of IL-6 were much lower in SHR than WKY, whereas both acute hypotension and plasma TNF peak were equivalent. We further explored in vitro the inflammatory response and showed that LPS-activated whole blood from SHR produced less TNF and IL-6 than WKY LPS-activated whole blood. Our results indicate that SHR have a greater ability to resist endotoxic shock than WKY. This is not related to their hypertension but is associated with an attenuated inflammatory response to LPS. (Hypertension. 1998;31:1350-1356.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID