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Vascular Hypertrophy (vascular + hypertrophy)
Selected AbstractsInduction of oxidative stress by homocyst(e)ine impairs endothelial function,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2001Vibhas S. Mujumdar Abstract Previous studies have demonstrated a relationship between hyperhomocysteinemia and endothelial dysfunction, reduced bioavailability of nitric oxide, elastinolysis and, vascular muscle cell proliferation. In vivo decreased nitric oxide production is associated with increased matrix metalloproteinase (MMP) activity and formation of nitrotyrosine. To test the hypothesis that homocysteine neutralizes vascular endothelial nitric oxide, activates metalloproteinase, causes elastinolysis and vascular hypertrophy, we isolated aortas from normotensive Wistar rats and cultured them in medium containing homocysteine, and calf serum for 14 days. Homocysteine-mediated impairment of endothelial-dependent vasodilatation was reversed by co-incubation of homocysteine with nicotinamide (an inhibitor of peroxinitrite and nitrotyrosine), suggesting a role of homocysteine in redox-mediating endothelial dysfunction and nitrotyrosine formation. The Western blot analysis, using anti-nitrotyrosine antibody, on aortic tissue homogeneates demonstrated decreased nitrotyrosine in hyperhomocysteinemic vessels treated with nicotinamide. Zymographic analysis revealed increased elastinolytic gelatinase A and B (MMP-2, -9) in homocysteine treated vessels and the treatment with nicotinamide decreases the homocysteine-induced MMP activation. Morphometric analyses revealed significant medial hypertrophic thickening (1.4,±,0.2-fold of control, P,=,0.03) and elastin disruption in homocysteine-treated vessels as compared to control. To determine whether homocysteine causes endothelial cell injury, cross-sections of aortas were analyzed for caspase activity by incubating with Ac-YVAD-AMC (substrate for apoptotic enzyme, caspase). The endothelium of homocysteine treated vessels, and endothelial cells treated with homocysteine, showed marked labeling for caspase. The length-tension relationship of homocysteine treated aortas was shifted to the left as compared to untreated aortas, indicating reduced vascular elastic compliance in homocysteine-treated vessels. Co-incubation of homocysteine and inhibitors of MMP, tissue inhibitor of metalloproteinase-4 (TIMP-4), and caspase, YVAD-CHO, improved vascular function. The results suggest that alteration in vascular elastin/collagen ratio and activation of MMP-2 are associated with decreased NO production in hyperhomocysteinemia. J. Cell. Biochem. 82:491,500, 2001. © 2001 Wiley-Liss, Inc. [source] Involvement of the renin,angiotensin system in the development of vascular damage in a rat model of arthritis: Effect of angiotensin receptor blockersARTHRITIS & RHEUMATISM, Issue 5 2010Takeo Sakuta Objective To explore the involvement of the renin,angiotensin system (RAS) in the development of vascular damage in adjuvant-induced arthritis (AIA) in rats. Methods Angiotensin II (Ang II; 0.25 or 1.0 mg/kg/day) was infused in control rats and rats with AIA for 21 days, and the impact of systemic inflammation on Ang II,induced hypertension, endothelial dysfunction, and vascular hypertrophy was evaluated. Expression of angiotensin II type 1 receptor (AT1R) and angiotensin-converting enzyme (ACE) in the aortas of rats with AIA were examined by real-time polymerase chain reaction (PCR) and Western blot analyses. Losartan (3 mg/kg/day) or irbesartan (5 mg/kg/day), both of which are AT1R blockers, was administered orally to rats with AIA for 21 days. In situ superoxide production in aortas was assessed according to the fluorogenic oxidation of dihydroethidium to ethidium. The expression and activity of NAD(P)H oxidases in aortas were examined by real-time PCR analysis and lucigenin chemiluminescence assay. Endothelial function in rats with AIA treated in vivo or ex vivo with AT1R blockers was also determined. Results The Ang II,induced hypertensive response, endothelial dysfunction, and vascular hypertrophy were exacerbated in rats with AIA. Expression of AT1R and ACE was increased in the aortas of rats with AIA. Both losartan and irbesartan decreased the levels of superoxide and the expression and activity NAD(P)H oxidases in the aortas of rats with AIA. The endothelial dysfunction in AIA was improved by the in vivo or ex vivo treatment with AT1R blockers. Conclusion The locally activated RAS is involved in the increased vascular oxidative stress and endothelial dysfunction in AIA. Our findings have important implications for clinical approaches to the reduction of cardiovascular risk in patients with rheumatoid arthritis. [source] 2421: Wall-to-lumen ratio of retinal vessels in patients with cerebrovascular damageACTA OPHTHALMOLOGICA, Issue 2010G MICHELSON Purpose There is evidence that generalized retinal arteriolar narrowing, which can be measured by the arteriole-to-venule ratio (AVR) of retinal vessels, predicts cerebrovascular events. The wall-to-lumen ratio (WLR) and wall cross-sectional area (WCSA) of retinal arterioles reflect structural arteriolar parameters. The primary objective was to test the association between WLR and AVR in patients with cerebrovascular damage. Methods In this cross-sectional study, 23 patients (57.5 +/- 9.4 years) with acute transitory ischemic attack or lacunar cerebral infarct were compared with two age-matched control groups: 83 subjects with essential hypertension (53.7 +/- 5.5 years) and 16 normotensive subjects (52.2 +/- 8.3 years). Retinal arteriolar parameters (WLR, WTH, and WCSA) were assessed in vivo with scanning laser Doppler flowmetry (SLDF). AVR and a qualitative evaluation of retinal vessels were obtained from digital retinal color photographs. The intima-media thickness (IMT) of the carotid artery was measured. Results WLR (0.44 +/- 0.1 vs. 0.34 +/- 0.1 vs. 0.30 +/- 0.1, P < 0.001) and carotid IMT (P < 0.05) were significantly greater in the cerebrovascular event group compared with normotensive subjects. WLR and WCSA were significantly higher in the cerebrovascular event group compared with subjects with mild arterial hypertension. AVR was similar in all three study groups. Conclusion The increase in WLR and WCSA of retinal arterioles, as well as in IMT in patients with cerebrovascular damage suggests vascular hypertrophy in the microvascular and macrovascular bed. The lack of association between AVR of retinal vessels and WLR of retinal arterioles [source] INVOLVEMENT OF PROLYLCARBOXYPEPTIDASE IN THE EFFECT OF RUTAECARPINE ON THE REGRESSION OF MESENTERIC ARTERY HYPERTROPHY IN RENOVASCULAR HYPERTENSIVE RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2009Xu-Ping Qin SUMMARY 1Previous studies indicate that rutaecarpine blocks increases in blood pressure and inhibits vascular hypertrophy in experimentally hypertensive rats. The aim of the present study was to determine whether the effects of rutaecarpine are related to activation of prolylcarboxypeptidase (PRCP). 2Renovascular hypertensive rats (Goldblatt two-kidney, one-clip (2K1C)) were developed using male Sprague-Dawley rats. Chronic treatment with rutaecarpine (10 or 40 mg/kg per day) or losartan (20 mg/kg per day) for 4 weeks to the hypertensive rats caused a sustained dose-dependent attenuation of increases in blood pressure, increased lumen diameter and decreased media thickness, which was accompanied by a similar reduction in the media cross-sectional area : lumen area ratio in mesenteric arteries compared with untreated hypertensive rats. 3Angiotensin (Ang) II expression was significantly increased in mesenteric arteries of hypertensive rats compared with sham-operated rats. No significant differences in plasma AngII levels were observed between untreated hypertensive and sham-operated rats. Hypertensive rats treated with high-dose rutaecarpine had significantly decreased Ang II levels in both the plasma and mesenteric arteries. 4Expression of PRCP protein or kallikrein mRNA was significantly inhibited in the right kidneys and mesenteric arteries of hypertensive rats. However, expression of PRCP protein and kallikrein mRNA was significantly increased after treatment with rutaecarpine or losartan (20 mg/kg per day). 5The data suggest that the repression of increases in systolic blood pressure and reversal of mesenteric artery remodelling by rutaecarpine may be related to increased expression of PRCP in the circulation and small arteries in 2K1C hypertensive rats. [source] Renal And Cardiac Sympathetic Baroreflexes In Hypertensive RabbitsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2001Geoffrey A Head SUMMARY 1. The purpose of the present study was to assess the changes to renal sympathetic nerve activity (RSNA) baroreflexes during the development of hypertension after renal clipping in conscious rabbits. 2. Rabbits were fitted with a clip on the right renal artery or underwent a sham operation under halothane anaesthesia. A recording electrode was implanted on the left renal nerve 1 week before the experiment, 3 or 6 weeks after the initial operation. During the experiment, drug-induced ramp rises and falls in mean arterial pressure (MAP) were used to produce RSNA and heart rate (HR) baroreflex curves. The RSNA for each experiment was calibrated against maximum RSNA evoked by stimulation of baroreceptor-independent trigeminal afferents. 3. Mean arterial pressure was 20 and 36% higher 3 and 6 weeks after clip implantation, respectively. Renal sympathetic nerve activity baroreflex curves were reset rightwards accordingly, but the shape of the RSNA curves was differentially affected. 4. At both hypertensive periods, MAP,HR baroreflex gain was markedly reduced due to a reduction in curvature. The HR baroreflex range was increased. The RSNA baroreflex gain was reduced at 3 weeks, which was due to a 35% lower RSNA baroreflex range, but was similar to sham animals at 6 weeks. 5. The results show that, in established two kidney, one clip hypertension in rabbits, the sympathetic baroreflex is relatively well preserved but sensitivity of cardiac baroreflexes is attenuated. Therefore, the short-term inhibition of RSNA baroreflexes is not related to the level of blood pressure or the development of secondary changes, such as cardiac or vascular hypertrophy, but may be related to circulating angiotensin, which is known to increase at this time. [source] | ||||||||||