Spontaneously Hypertensive Rats

When groups of 10 Spontaneously Hypertensive Rats (SHR) were fed diets containing either 1% w/w regular garlic (Allium sativum) (AS) or 1% w/w wild garlic (Allium ursinum) (AU) for 45days, the final mean systolic blood pressure (SBP) was reduced significantly compared to control (C) (C 189; AS 175; Au 173 mm Hg). Compared to C, body weight and circulating glucose and triglyceride levels were not significantly different; but circulating insulin was significantly higher (C 23.6; AS33.9; AU 29.5 uIU/dl), and total cholesterol was significantly lower (C 133; AS 115; AU117 mg/dl) in the two groups consuming AS or AU. HDL rose in the two garlic groups, but the differences from C were statistically significant only for the AU group. In a second study, the effects of a lower dose of dietary AS and AU (0.1% w/w) on SBP and various blood chemistries were compared head-to-head in 80SHR — 40 control and 40 test rats. Both AS and AU decreased SBP significantly compared to a control group of 10 SHR followed simultaneously. However, AU at this lower concentration produced a significantly greater SBP-lowering effect compared to the AS group. In addition, AU decreased total cholesterol significantly and tended to increase HDL compared to AS. Accordingly, the results suggest that AU has a greater therapeutic benefit compared to AS at a given concentration.

Winged bean seed (WBS) is an underutilized tropical crop. The current study evaluates its potential to reduce blood pressure (BP) in spontaneously hypertensive rats and finds that it reduces BP significantly, in a dose-dependent manner. Five peptides with the sequences, RGVFPCLK, TQLDLPTQ, EPALVP, MRSVVT and DMKP, have been characterized in terms of their stability against ACE via in vitro and in silico modelling. All peptides exhibited IC50 values between 0.019 and 6.885 mM and various inhibitory modes, including substrate, prodrug and true inhibitor modes. The toxicity status of non-Current Good Manufacturing Practice (non-CGMP) peptides is evaluated and the results show that such peptides are toxic, and thus are not suitable to be tested in animals, particularly in repeated-dose studies. In short, WBS hydrolysate demonstrated in vitro ACE inhibitory properties and in vivo blood pressure lowering efficacy in rat models, fostering its potential as a functional food ingredient. Non-CGMP grade peptides are toxic and unfit for testing in animal models.

Abstract. When groups of 10 Spontaneously Hypertensive Rats (SHR) were fed diets containing either 1% w/w regular garlic (Allium sativum) (AS) or 1% w/w wild garlic (Allium ursinum) (AU) for 45 days, the final mean systolic blood pressure (SBP) was reduced significantly ...

Genetic factors that predispose to hypertension may contribute to element disturbances observed in hyperten-sive patients. We tested the hypothesis that the deletion allele of the angiotensin-converting enzyme (ACE) gene is associated with element imbalances in hypertension. The concentrations of elements in genetically predisposed to hypertension rats (SHRs) and their controls (WKY rats) were also examined. ICP-MS was used for elemental analysis of human hair and animal fur. Genotyping was performed by PCR. We also measured micronuclei frequency and distribution of peripheral blood leukocytes in cell cycle phases by flow cytometry and studied the correlations of these parameters with element contents. In general, the tendency for higher levels of toxic and lower levels of essential elements is observed in hypertension, specifically in patients carrying the D allele. Hypertensive men had significantly higher Be, V, Cr, As, Mo, Ag, Sb, and Na levels and lower Ca, Zn, Ba, and U levels compared with control subjects; the differences were not significant for Mg, Al, K, Mn, Fe, Co, Ni, Cu, Se, Cd, Tl, Pb, and Th. The D allele was associated with higher Be, Mo, and Th levels and lower Zn, Se, and Tl levels. The concentrations of Ca, Co, Mo and U were higher in SHR than those in the WKY rats. Mo, an antagonist of Cu, positively correlated with the S-phase cells, and Cu positively correlated with micronuclei frequency. The results suggest an involvement of the ACE I/D polymorphism in element imbalances in hypertension and attract attention to the possible significant role of genetic factors in Mo accumulation.

The medullary portion of the kidney plays a crucial role in the control of sodium and water excretion and arterial pressure. This control is anomalous in hypertension and may be related to an impaired renal nitric oxide (NO) production. We have measured the activity of NO synthase (NOS) in the renal medulla, renal cortex, heart, and aorta from normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Enzyme activity was determined by measuring the conversion of 4C-C-L-arginine to 4C-C-L-citrulline. Ca+-d-dependent NOS activity was considerably higher in the renal medulla than in the other tissues studied, both in WKY and SHR. The medulla and heart of the SHR displayed a higher Ca+-d-dependent NOS activity compared to that of WKY. No differences were found in the Ca+-i-independent NOS activity, except for the renal cortex of the SHR, which was higher than in the rest of the tissues. These observations indicate that the renal medulla has a higher relative capacity to synthesize NO and suggest that the impaired renal medullary control of arterial pressure of genetic hypertension is not due to a reduced NO production by the kidney.

Previously we reported that in vivo exposure to ambient particulate matter (PM) induces vasodilatation in rat aorta. The purpose of the current study was to investigate the intracellular messengers involved in PM-elicited vasodilatation in aortas from spontaneous hypertensive (SHR) and normotensive (WKY) rats. METHODS: The contribution of three different intracellular pathways, i.e. (1) the NO-cGMP pathway, (2) prostanoids signaling and

The sympathetic preganglionic neurons (SPN) of the intermediolateral cell column (IML) play a critical role in the maintenance of vascular tone. We undertook a comparative neuroanatomical analysis of neuronal nitric oxide synthase (nNOS) expression in the SPN of the mature normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rat (SHR). The anatomical relationship between nNOS and the NO signaling molecule cyclic guanosine monophosphate (cGMP) was also determined. All animals were male, age >6 months. Fluorogold (FG) retrograde labeling of SPN (detected with immunohistochemistry) was combined with NADPH-diaphorase histochemistry for NOS in the thoracic spinal cord (T1–11, n = 5 WKY, 5 SHR). There was no difference in the total number of FG-labeled SPN (WKY 6,542 ± 828, SHR 6,091 ± 820), but the proportion of FG-labeled cells expressing NOS was significantly less in the SHR (WKY 64.4 ± 5.1 vs. SHR 55.6 ± 2.1, P < 0.05). Fluorescence immunohistochemistry for nNOS/cGMP (n = 4 WKY, 4 SHR) was also performed. Confocal microscopy revealed that all nNOS-positive SPN contain cGMP and confirmed a strain-specific anatomical arrangement of SPN cell clusters. A novel subpopulation of cGMP-only cells were also identified. Double labeling for cGMP and choline acetyltransferase (n = 3 WKY, 3 SHR), confirmed these cells as SPN in both WKY and SHR. These results suggest that cGMP is a key signaling molecule in SPN, and that a reduced number of NOS neurons in the SHR may play a role in the increase in sympathetic tone associated with hypertension in these animals. J. Comp. Neurol. 497:566–574, 2006. © 2006 Wiley-Liss, Inc.

The aims of this study were to investigate the effects of melatonin and n-acetylcysteine on the baroreflex sensitivity and to verify whether those effects were correlated with their antioxidant capacity in Wistar-Kyoto and spontaneously hypertensive rats (SHR). Rats were treated with 30 mg/kg/day of melatonin or 4 g/kg/day of n-acetylcysteine for 4 weeks. Changes in mean arterial pressure, heart rate, plasma norepinephrine, and epinephrine were measured in conscious rats after an intravenous injection of phenylephrine or sodium nitroprusside. The SHR were characterized by decreased reflex chronotropic responses to phenylephrine and sodium nitroprusside (P &lt; .001 and P &lt; .001), as well as by an enhanced increase in plasma catecholamine concentrations in response to sodium nitroprusside (P &lt; .001). Melatonin and n-acetylcysteine produced a significant reduction in mean arterial pressure and heart rate in SHR (P &lt; .001). Melatonin and n-acetylcysteine improved bradycardic (...

The premise that the intrinsic level of expression of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase determines the relative sensitivity to the serum cholesterol raising action of dietary cholesterol was examined in 9 strains of rat. For further comparison purposes, hamsters were also examined. The basal expression of hepatic HMG-CoA reductase, extent of feedback regulation by cholesterol, and changes in serum cholesterol levels and the hepatic low-density lipoprotein (LDL) receptor in response to cholesterol challenge were determined in these animals. The Sprague-Dawley, Wistar-Furth, Spontaneously Hypertensive, Lewis, and Wistar-Kyoto rats were all very resistant to dietary cholesterol and exhibited hepatic HMG-CoA reductase activities above 150 pmol / min(-1) / mg(-1). The Buffalo, Brown Norway, and Copenhagen 2331 rats had hepatic HMG-CoA reductase activities below 90 pmol / min(-1) / mg(-1) and had increases in serum cholesterol levels ranging from 12 to 33 m...

The initial observation that taurine (T) prevented stroke in stroke-prone spontaneously hypertensive rats (SHRSP) led us to study the effects of T on cardiovascular diseases (CVD), as well as the epidemiological association of T and mortality rates, by using the data from WHO-coordinated Cardiovascular Disease and Alimentary Comparison Study, which covered 61 populations in 25 countries. In this study, 24 hour urine (24-U) samples were examined along with biomarkers of CVD risk. The mortality rate from ischemic heart disease (IHD), which was lowest among the Japanese compared to the populations of other developed countries, was positively related to total serum cholesterol (TC) and inversely related to 24-U taurine excretion (24-UT), as well as the n-3 fatty acid to total phospholipids ratio of the plasma membrane, both biomarkers of seafood intake. Analysis of 5 diet-related factors revealed that TC and BMI were positively associated with IHD mortality in both genders while Mg and ...

In spite of a significant improvement in control of numerous predisposing risk factors, stroke remains a major health problem and a common cause of death and disability in our societies. Genetic predisposition to stroke development exists and has been documented in both animal models and in humans. However, a precise definition of genetic factors responsible for common forms of stroke is still lacking, mainly due to its complex nature, the confounding presence of other predisposing risk factors, and the genetic heterogeneity of human populations. In contrast, important breakthroughs have been reached for monogenic forms of stroke, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). An animal model of stroke, the stroke-prone spontaneously hypertensive rat, has provided valuable information on genetic factors involved in stroke predisposition. Among them, the gene-encoding atrial natriuretic peptide has been identified as a st...

Pressure overload of the heart is associated with a perturbed gene expression of the cardiomyocyte leading to an impaired pump function. The ensuing neuro-endocrine activation results in disordered influences of angiotensin II and catecholamines on gene expression. To assess whether angiotensin II type 1 receptor inhibition can also counteract a raised sympathetic nervous system activity, spontaneously hypertensive rats fed a hypercaloric diet were treated with eprosartan (daily 90 mg/kg body wt) and cardiovascular parameters were monitored with implanted radiotelemetry pressure transducers. Both, blood pressure and heart rate were increased (p &lt; 0.05) by the hypercaloric diet. Although eprosartan reduced (p &lt; 0.05) the raised systolic and diastolic blood pressure, the diet-induced rise in heart rate was blunted only partially. In addition to drugs interfering with the enhanced catecholamine influence, compounds should be considered that selectively affect cardiomyocyte gene e...

We have demonstrated that spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells (VSMC) show the exaggerated growth and produce angiotensin II (Ang II). In the current study, we investigated the role of endogenous Ang II in the regulation of the cell cycle in VSMC from SHR. Levels of Ang II in conditioned medium from SHR-derived VSMC cultured without serum were significantly higher than levels in conditioned medium from Wistar-Kyoto (WKY) rat-derived VSMC. Basal DNA synthesis was higher in quiescent VSMC from SHR than that in cells from WKY rats. An Ang II type 1 receptor antagonist, CV11974, significantly inhibited the elevation in DNA synthesis in quiescent VSMC from SHR but did not affect it in cells from WKY rats. Cellular DNA content analysis by flow cytometry revealed that the proportion of cells in S phase was higher, whereas the proportion of cells in G1+G0 phase was lower in VSMC from SHR than those in cells from WKY rats. CV11974 significantly decreased...