Myrtus communis improves cognitive impairment in renovascular hypertensive rats.

Myrtus communis has anti-inflammatory, neuroprotective and anticholinesterase activities yet there have been limited studies examining effects of Myrtus communis on cognitive functions. This study investigated the possible effects of Myrtus communis on changes in the cognitive functions of experimental renovascular hypertensive rats. Fifty-six Wistar-Albino rats were equally divided into 4 groups; sham-operated control, renovascular hypertension (RVH), ramipril (RVH + Ram) and Myrtus communis extract (RVH + MC) treatment groups. Goldblatt's 2-kidney 1-clip (2K1C) method was used to induce RVH. At the end of 9 weeks of treatment, after blood pressure recording, the animals underwent new object recognition test and Morris water maze (MWM) task. Following these tests, blood brain barrier (BBB) integrity was examined in 6 animals from each group. In the others after decapitation, osteopontin and interleukin (IL)-10 levels were measured in blood samples; while matrix metalloproteinase (MMP)-13, sodium potassium adenosine triphosphatase (Na+,K+-ATPase), cluster of differentiation (CD) 36, amyloid beta (Aß), neprilysin levels, and acetylcholinesterase (AChE) activity were investigated in hippocampal tissues. In RVH group, high systolic blood pressure decreased serum IL-10 levels, increased serum osteopontin levels and also impaired BBB permeability. Hippocampal MMP-13, CD36, Aß, neprilysin levels and AChE activities were elevated, while there were decreases in Na+,K+-ATPase levels. In new objet recognition test, discrimination index (DI) was determined as lower in saline-treated RVH group compared to control animals. In MWM training trail, 4th day performance in finding platform was significantly reduced in saline-treated RVH group compared to control group. RVH also decreased the time spent in target quadrant in probe test of MWM task compared to control group. In both of the treatment groups, all biochemical parameters were restored in parallel with improvement in the behavioral test performances. The results of this study suggest that Myrtus communis extract may improve the cognitive dysfunctions in hypertension through antihypertensive, anti-inflammatory and anticholinesterase activities.

Effect of chrysanthemum extract on myocardial fibrosis in rats with renovascular hypertension.

OBJECTIVE: To investigate the inhibitory effect of chrysanthemum extract on myocardial fibrosis in rats with renovascular hypertension, and explore the possible mechanism underlying this effect. METHODS: Sixty Wistar rats were randomly divided into six groups: sham operation, model, positive control, and low-, medium-, and high-dose Huai chrysanthemum extract groups (ten rats per group). With the exception of the sham operation group, a renal hypertensive model was established in rats using the ""two-kidney, one clip"" method. After 6 weeks, low-, medium-, and high-dose groups were intragastrically administered chrysanthemum extract at 1, 2, or 4 g/kg, respectively, once daily for 4 weeks. The positive control group was administered Kato Pury at 50 mg/kg once daily for 4 weeks, while sham operation and model groups received an equal volume of distilled water once daily for 4 weeks. Blood pressure changes were examined before modeling, 6 weeks after modeling, and after 4 weeks of treatment administration. Ventricular remodeling indexes were measured by high frequency echocardiography after 4 weeks of treatment administration. Pathological changes were observed by hematoxylin and eosin, and Masson's trichrome staining methods. Collagen typeⅠ (Col Ⅰ) and type Ⅲ (Col Ⅲ) expression were examined by enzyme-linked immunosorbent assays. Transforming growth factor-ß1 (TGF-ß1), sma mad 3 (Smad3), Smad7, Ras homolog gene family, member A (RhoA), and Rho-associated protein kinase 1 (ROCK1) protein expression were detected by Western blot. RESULTS: Compared with the model group, chrysanthemum-administered groups and the positive control group showed significant improvement of arterial blood pressure, echocardiography indicators, and degree of myocardial fibrosis (P < 0.05). In addition, these groups exhibited decreased expression of Col Ⅰ, Col Ⅲ, RhoA, ROCK1, TGF-ß1, and Smad3, and increased Smad7 expression. Such improvements were most obvious in the high-dose chrysanthemum extract group (P < 0.05). CONCLUSION: Chrysanthemum extract could effectively reduce myocardial fibrosis in rats with renovascular hypertension by a mechanism that potentially involves inhibition of RhoA/ROCK1 and TGF-ß1/Smad signaling pathways.

Hydrogen Sulfide Improves Myocardial Remodeling via Downregulated Angiotensin â ¡/AT1R Pathway in Renovascular Hypertensive Rats.

BACKGROUND: Hydrogen sulfide (H2S) is an important endogenous gaseous transmitter in many physiological functions. Plasma H2S decreased, and angiotensin II (Ang II) type 1 receptor (AT1R) increased in the myocardial tissues in 2-kidney 1-clip (2K1C) rats than in normotensive rats. Accumulating evidences suggest that H2S inhibited Ang II/AT1R pathway to regulate cardiovascular function. Therefore, we hypothesized that H2S may exert beneficial effects on myocardial remodeling in 2K1C rat models of renovascular hypertension. METHODS AND RESULTS: Sodium hydrosulfide (NaHS, 56 µmol/kg/day) was administered intraperitoneally to the rats from the 7th day after 2K1C operation. Systolic blood pressure was significantly increased from the first week after the operation and was lowered after NaHS treatment for 4 weeks. H2S could also inhibit the ratio of left ventricle and septum weight to body weight, improve cross-sectional area, and ameliorate ventricular dysfunction. Additionally, the protein expression of AT1R and Ang II serum content were downregulated, whereas superoxide dismutase (SOD) protein was upregulated in 2K1C rats by NaHS treatment for 4 weeks. Furthermore, the reactive oxygen species level and AT1R protein were increased, whereas SOD protein was decreased in cardiomyocytes treated with Ang II compared with the control group. NaHS could reverse these changes. Losartan and N-acetylcysteine could also reverse Ang II-induced changes. CONCLUSIONS: The protective effect of H2S is attributable to the suppression of oxidative stress. This process involves the inhibition of the Ang II/AT1R pathway and upregulation of antioxidant enzymes in 2K1C rats.

[Molecular mechanism by which green tea and tea extract inhibits left ventricle hypertrophy induced by renovascular hypertension in rats].

OBJECTIVE: To investigate the preventive effects and the molecular mechanism of tea and tea extracts (polyphenols and EGCG) on left ventricle hypertrophy (LVH) induced by Renovascular hypertension in rats. METHODS: One hundred and sixty male Wistar rats were randomly divided into five groups: negative control group (SHAM), operation group (2K1C), green tea group (2K1C + GT), tea polyphenol group (2K1C + TP), EGCG group (2K1C + EGCG). After surgery operation, rats in different groups received tap water, tap water, 2% green tea, 0.1% tea polyphenol and 0.05% EGCG respectively, as the sole drinking source for 8 weeks until the end of the experiment. RESULTS: The results showed that the blood pressure, the ratio of left ventricle weight to body weight (LVW/BW) and the left ventricular wall thicknesses (LVWT) in 2K1C group significantly increased (P < 0.01), when compared to those in sham operation group. However, when compared to these parameters in operation group, the ratio of LVW/BW and HW/BW in green tea group, tea polyphenols group and EGCG group significantly decreased (P < 0.05), while the activities of GSH-Px and SOD increased, and the levels of ROS in heart were also significantly decreased (P < 0.05). Ras, P-ERK protein expressions in tea-treatment groups were also decreased. CONCLUSION: Green tea, tea polyphenols and EGCG can attenuate the development of left ventricular hypertrophy induced by renal hypertension in rats. The possible mechanisms may be due to its antioxidant properties and the modulation of Ras-to-MAPKs mediated signal transduction.

[Effect of tianma gouteng recipe on interfering LV and aortic hypertrophy in renovascular hypertension rats].

OBJECTIVE: To investigate the effect of Tianma Gouteng recipe (TGR) on interfering left ventricular (LV) and aortic hypertrophy and tissue angiotensin II (Ang II) in rats with renovascular hypertension. METHOD: The animal model of renovascular hypertension was used in this experiment. Hypertensive rats were randomly allocated into model group, Enalapril group and TGR group, and the drugs were used for 6 weeks continuously. During this period, the blood pressure of rats was measured every two weeks. After rats were sacrificed, the wet weight, tissue Ang II level of LV and aorta, and the cardiac index were measured. RESULT: One week after renovascular stenosis, the systolic blood pressure (SPS) of model group was increased by 37.4 mmHg, and 7 weeks after stenosis, the LV and aortic hypertrophy was obvious increased, meanwhile, tissue Ang II of LV and aorta was raised markedly (P < 0.01). Contrasting with the model group, blood pressure was reduced and the morphological index was improved in Enalapril group respectively (P < 0.05 or P < 0.01); the wet weight of LV and aorta were reduced, the morphological index was improved, the rise of Ang II in tissue was suppressed, in TGR group significantly. CONCLUSION: TGR can attenuate myocardial and aorta hypertrophy induced by renovascular hypertension, and suppress the rise of Ang II in tissue significantly. This suggests that TGR has the effects on interfering LV and aortic hypertrophy by an independent-antihypertensive way.

Hypercholesterolemia and hypertension have synergistic deleterious effects on coronary endothelial function.

OBJECTIVE: Coronary endothelial dysfunction is associated with an increase in cardiac events. Hypercholesterolemia (HC) and hypertension (HT) are both associated with endothelial dysfunction, and their coexistence is associated with an increased incidence of cardiac events in epidemiological studies. However, pathogenic mechanisms are poorly understood. Here we studied the effects of coexisting HC and HT on coronary endothelial function. METHODS AND RESULTS: Four groups of pigs were studied after 12 weeks of a normal diet (n=9), a 2% HC diet (n=9), HT (achieved by unilateral renal artery stenosis, n=8), or HC+HT (n=6). Coronary endothelial function was tested, in epicardial arteries and arterioles, by using organ chamber techniques. Oxidative stress was measured in coronary artery tissue. Vasodilatory response to bradykinin and calcium ionophore was significantly impaired in animals with HC+HT compared with each risk factor alone (P<0.05 for both). In animals with coexistent HC and HT, the increase in oxidative stress was more pronounced compared with each risk factor alone (P<0.05). Furthermore, chronic antioxidant supplementation significantly improved coronary artery vasoreactivity. CONCLUSIONS: These results suggest that HC and HT have a synergistic deleterious effect on coronary endothelial function, associated with increased oxidative stress. This interaction may contribute to the increased incidence of coronary heart disease and cardiac events seen when HC and HT coexist.

[Study on the effect of zhimu combined huangqi on improving renal hypertension rat's cardiac dysfunction].

OBJECTIVE: To observe the effect of Zhimu and Huangqi used singly or combinatively on improving experimental cardiac dysfunction, and mainly to observe zhimu's effect on restraining sympathetic nerve and blocking beta-adrenergic-recepter and huangqi's effect of improving hemodynamics on heart failure. METHOD: Two-clib one kidney operation was done to make renal hypertension rat model, 8 weeks after operation, rats were divided into groups and medicated for 6 weeks, and then their heart rate and blood pressure were measured, left ventricle was cannulated to estimate heart function, and heart-weight-index and left-ventricle-weight-index were measured. RESULT: Zhimu could slow rats heart rate obviously, prevent cardiac remodeling, but did not affect cardiac function remarkably; Huangqi could reduce blood pressure, heighten +dp/dtmax and -dp/dtmax remarkably; the combined use of the two drugs could decrease plasma catecholamine concentration, adjust myocardium cAMP content, and improve heart function obviously. CONCLUSION: Zhimu and Huangqi can protect experimental cardiac dysfunction, and the combined use is better than the single use, which shows it better to use the two drugs combinatively in treating heart dysfunction.

[Effect of praeruptorum caumarin on cardiac mass, myocardial [Ca2+]i and Na+, K(+)-ATPase, Ca2+, Mg(2+)-ATPase activity in renovascular hypertensive rats].

AIM: To investigate the preventive and reversional effect of praeruptorum caumarin compound on left ventricular hypertrophy in renovascular hypertensive rats (RHR) and its mechanism. METHODS: The two-kidney-one-clip (2K1C) RHR model was used. The blood pressure, wet weight of the left ventricle, surface area of myocardial cells, resting [Ca2+]i level and Na+, K(+)-ATPase, Ca2+, Mg(2+)-ATPase activity of myocardial membrane and mitochondria were measured. RESULTS: Praeruptorum caumarin 30 mg.kg-1.d-1 was given ig for 9 weeks from the 6th or 9th week after operation in the preventive or regressive group. The blood pressure, left ventricle wet weight and area of myocardial cells of the preventive and regressive group were significantly reduced than that of the LVH group. The resting [Ca2+]i of the both praeruptorum caumarin treated groups (121 +/- 13, 133 +/- 9 nmol.L-1) were lower than that of the LVH group (158 +/- 7 nmol.L-1). The KCl-induced [Ca2+]i elevation was decreased more significantly in preventive and regressive group than that of the hypertrophic myocytes. The activity of Na+, K(+)-ATPase and Ca2+, Mg(2+)-ATPase increased by 40% and 93% in the preventive group, 28.4% and 48.8% in regressive group than that of the LVH group. CONCLUSION: Praeruptorum caumarin was shown to prevent and reverse hypertrophy of LVH by lowering [Ca2+]i and increasing the ATPase activity.

Effects of praeruptorine C on the intracellular free calcium in normal and hypertrophied rat ventricular myocytes.

AIM: To study the intracellular free calcium ([Ca2+]i) in normal and hypertrophic left ventricular myocytes isolated from adult rat hearts and the effects of praeruptorine C (Pra-C) on them. METHODS: [Ca2+]i of single myocyte was measured with Fura 2-AM. RESULTS: The resting [Ca2+]i was 87 +/- 4 nmol.L-1 in normal left ventricular myocytes, 123 +/- 7 nmol.L-1 in hypertrophied myocytes. After exposure to KCl (20, 40, and 60 mmol.L-1), the [Ca2+]i were increased by 66%, 141%, and 268% in normal myocytes, and 77%, 185%, and 243% in hypertrophic myocytes, respectively. Pra-C (1, 10, and 100 mumol.L-1) concentration-dependently inhibited the [Ca2+]i elevation caused by KCl (35 mmol.L-1) or norepinephrine (20 mumol.L-1) in both normal and hypertrophied myocytes. All of the effects of Pra-C were similar to that of nifedipine. CONCLUSION: [Ca2+]i of hypertrophied myocytes was higher than that of normal ones and Pra-C decrease the [Ca2+]i elevation in left ventricular myocytes resulted from its calcium channel blockade.

Effects of nisoldipine on hypertension and glomerulosclerosis in Cohen diabetic rat with Goldblatt hypertension.

Nisoldipine treatment for five months prevented a rise in blood pressure in Cohen diabetic rats with Goldblatt hypertension, compared to a significant elevation in untreated controls. Blood creatinine and urea also decreased significantly in the treated animals, and renal lesions were less severe. The prevalence of glomerulosclerosis, however, remained unaltered in both the treated and control groups. These findings indicate that increased blood pressure aggravates renal changes, while reducing it eliminates the aggravation.

Renal uptake of Tl-201 in hypertensive patients undergoing myocardial perfusion imaging.

The detection of renovascular disease (RVD) has particular relevance in hypertensive patients (HP) who have symptoms of target organ damage. To evaluate the possibility of RVD in HP undergoing myocardial perfusion scintigraphy for chest pain symptoms, posterior renal images were obtained at 1-3 hours after Tl-201 injection. Analog and computer images were obtained for 5 minutes in 45 HP; 12 patients with no history of hypertension or renal disease served as normal controls. For qualitative analysis, images were coded and read by three observers as to symmetry of renal uptake. Differential renal uptake of Tl-201 (DRU) was quantitated on computer images. In normal controls, uptake was agreed on as symmetric. In HP, 6 patients had marked asymmetry of DRU and 4 had possibly significant asymmetry; 2 had decreased uptake in both kidneys suggesting bilateral RVD or nephrosclerosis. Objective correlation with DRU was obtained in 10 HP who had contrast angiography, confirming 4 cases of unilateral RVD and 2 of bilateral RVD. Thirteen patients also had renography with Tc-99m DTPA; differential renal function by this modality correlated well with DRU of Tl-201 (r = 0.98). Thus, DRU of Tl-201 can be used as a supplement to myocardial scintigraphy to identify HP who require further evaluation and treatment of RVD.

Effects of a Japanese medicinal plant on the rat subtotal nephrectomy model: evaluation of its effect by microvascular casts.

Effects of a Japanese medicinal plant named Sairei-To, were examined in a rat experimental renal disease. Thirteen weeks after subtotal nephrectomy, the blood pressures in rats given Sairei-To (Sairei-To rats) were lower than those without Sairei-To. The urinary protein excretions and glomerular sclerosis were markedly decreased in the Sairei-To treated rats. Arteriolar diameters were measured using microvascular casts. The afferent and efferent arterioles were both significantly dilatated. The efferent arterioles in Sairei-To rats were dilated to a greater extent than that of the afferent. These results indicated that Sairei-To lessened renal damages in the rat subtotal nephrectomy model, possibly through the blood pressure reduction and the efferent arteriolar dilatation.

Antihypertensive drug therapy prevents cerebral microvascular abnormalities in hypertensive rats.

Studies were performed on anesthetized 16-18 week old normotensive Wistar-Kyoto rats, spontaneously hypertensive rats, and Goldblatt two-kidney one clip renal hypertensive rats, treated from age 4-5 weeks with an oral antihypertensive regimen consisting of hydralazine, reserpine, and chlorothiazide. Measurements of flow and intravascular pressure in the cerebral microvasculature were made via a constantly suffused open cranial window using video microscopy. A significant upward shift was seen in the pressure range for cerebral blood flow autoregulation in both groups of untreated hypertensive animals. Following treatment, the autoregulatory range in both hypertensive models was restored to a level nearly identical to control. The prevention of this shift in treated animals was due primarily to the prevention of structural microvascular adaptations that occur in untreated hypertensive animals. By preventing elevations in microvascular pressure, treatment may have eliminated the major stimulus for development of hypertrophy in resistance vessels. However, a persistent increment of arteriolar wall mass in treated spontaneously hypertensive rats may represent a hyperplastic response not influenced by treatment. Likewise, a persistent constriction of the smallest arterioles in treated renal hypertensive rats may represent a differential sensitivity of microvessels to circulating vasoactive agents. It appears that treatment initiated in the prehypertensive state, or before significant sustained hypertension has occurred, can markedly reduce the cerebrovascular morbidity associated with two different forms of hypertension.