scholarly journals The Impact of Combined Treatment with Atorvastatin and Amlodipine in Stroke-prone Spontaneously Hypertensive Rats

Author(s):  
Kanako Muraga ◽  
Chikako Nito ◽  
Masayuki Ueda ◽  
Toshiki Inaba ◽  
Tomonari Saito ◽  
...  
2020 ◽  
Vol 61 (1) ◽  
pp. 128-137 ◽  
Author(s):  
Shin-Huei Liu ◽  
Chun-Ting Lai ◽  
Hau-Ruey Chen ◽  
Wei-Lun Lin ◽  
Shinya Yamada ◽  
...  

2013 ◽  
pp. 471-478 ◽  
Author(s):  
M. BENCZE ◽  
M. BEHULIAK ◽  
J. ZICHA

Most anesthetics induce characteristic hemodynamic changes leading to blood pressure (BP) reduction but the role of renin-angiotensin system (RAS), sympathetic nervous system (SNS) and nitric oxide (NO) synthesis in this BP reduction is unknown. We therefore studied the influence of four widely used anesthetics – pentobarbital (P), isoflurane (ISO), ketamine-xylazine (KX) and chloralose-urethane (CU) – on the participation of these vasoactive systems in BP maintenance. BP effects elicited by the acute sequential blockade of RAS (captopril), SNS (pentolinium) and NO synthase (L-NAME) were compared in conscious and anesthetized Wistar or spontaneously hypertensive rats (SHR). Except for pentobarbital all studied anesthetics evidenced by diminished BP responses to pentolinium. The absolute pentolinium-induced BP changes were always greater in SHR than Wistar rats. KX anesthesia eliminated BP response to pentolinium and considerably enhanced BP response to NO synthase inhibition in SHR. In both rat strains the anesthesia with ISO or CU augmented BP response to captopril, decreased BP response to pentolinium and attenuated BP response to NO synthase inhibition. In conclusion, pentobarbital anesthesia had a modest influence on BP level and its maintenance by the above vasoactive systems. Isoflurane and chloralose-urethane anesthesia may be used in cardiovascular experiments if substantial BP decrease due to altered contribution of RAS, SNS and NO to BP regulation does not interfere with the respective research aim. Major BP reduction (namely in SHR) due to a complete SNS absence is a major drawback of ketamine-xylazine anesthesia.


2017 ◽  
Vol 10 (1) ◽  
pp. 18-24
Author(s):  
Stancho S. Stanchev ◽  
Alexandar A. Iliev ◽  
Lina G. Malinova ◽  
Boycho V. Landzhov ◽  
Georgi N. Kotov ◽  
...  

SummaryThe impact of hypertension on the kidney is associated with a number of morphological changes, which gradually lead to development of end-stage kidney disease. The aim of the present study was to trace the postnatal histological changes in the morphology of nephrons and renal interstitium in spontaneously hypertensive rats. In this study, we described and compare alterations in renal histology as a consequence of hypertension in two age groups of spontaneously hypertensive rats, aged 2 and 6 months (n=3; per age group). The description of the alterations in renal morphology was made by light microscopic analysis using routine haematoxylin and eosin staining, periodic acid Schiff (PAS) reaction and Mallory’s trichrome staining. We did not observe significant changes in renal histology in 2-month-old rats: renal corpuscles were relatively well preserved, proximal and distal tubules were clearly demarcated, and no pathological changes in the larger intrarenal blood vessels were found. There was evidence of glomerular and tubular basement membranes thickening and focal interstitial fibrosis. In 6-month-old rats, we noted pronounced glomerulosclerosis, periglomerular and periarteriolar fibrosis and expansion of interstitial fibrosis. The vascular alterations depended on the size of the blood vessels and included hyaline arteriosclerosis, fibrinoid necrosis and myointimal thickening of interlobular arteries. Untreated hypertensive nephrosclerosis is associated with progressive renal alterations, which cause impaired renal function – a lifelong limiting factor.


2005 ◽  
Vol 98 (2) ◽  
pp. 572-578 ◽  
Author(s):  
Joseph A. Beatty ◽  
Jeffery M. Kramer ◽  
Edward D. Plowey ◽  
Tony G. Waldrop

Recently, physical exercise has been shown to significantly alter neurochemistry and neuronal function and to increase neurogenesis in discrete brain regions. Although we have documented that physical exercise leads to molecular changes in the posterior hypothalamic area (PHA), the impact on neuronal activity is unknown. The purpose of the present study was to determine whether neuronal activity in the PHA is altered by physical exercise. Spontaneously hypertensive rats (SHR) were allowed free access to running wheels for a period of 10 wk (exercised group) or no wheel access at all (nonexercised group). Single-unit extracellular recordings were made in anesthetized in vivo whole animal preparations or in vitro brain slice preparations. The spontaneous firing rates of PHA neurons in exercised SHR in vivo were significantly lower (8.5 ± 1.6 Hz, n = 31 neurons) compared with that of nonexercised SHR in vivo (13.7 ± 1.8 Hz, n = 38 neurons; P < 0.05). In addition, PHA neurons that possessed a cardiac-related rhythm in exercised SHR fired significantly lower (6.0 ± 1.8 Hz, n = 11 neurons) compared with nonexercised SHR (12.1 ± 2.4 Hz, n = 18 neurons; P < 0.05). Similarly, the spontaneous in vitro firing rates of PHA neurons from exercised SHR were significantly lower (3.5 ± 0.3 Hz, n = 67 neurons) compared with those of nonexercised SHR (5.6 ± 0.5 Hz, n = 58 neurons; P < 0.001). Both the in vivo and in vitro findings support the hypothesis that physical exercise can lower spontaneous activity of neurons in a cardiovascular regulatory region of the brain. Thus physical exercise may alter central neural control of cardiovascular function by inducing lasting changes in neuronal activity.


2021 ◽  
Vol 12 ◽  
Author(s):  
Iwona Baranowska ◽  
Olga Gawrys ◽  
Malwina M. Roszkowska-Chojecka ◽  
Bozena Badzynska ◽  
Dagmara Tymecka ◽  
...  

The contribution of chymase, one of the enzymes responsible for angiotensin II generation in non-ACE pathway, remains unclear in the development of hypertension. The aim of the study was to investigate chymase inhibition as potential antihypertensive therapy in spontaneously hypertensive rats (SHR). To block chymase we employed chymostatin, a commercial inhibitor, and new analogues of rapeseed-derived peptides, VWIS and RIY. These simple and easy to obtain peptides not only block chymase, but also possess weak activity to inhibit ACE. This is a first attempt to evaluate the impact of chronic administration of selected inhibitors on blood pressure of SHR in two phases of hypertension. Male SHR (6 or 16 weeks old) were treated daily for two weeks with chymostatin (CH; 2 mg/kg/day), the peptides VWIS (12.5 mg/kg/day) or RIY (7.5 mg/kg/day); control groups received chymostatin solvent (0.15% DMSO in saline) or peptide solvent (saline). The substances were administered intravenously to conscious animals via a chronically cannulated femoral vein. Systolic blood pressure (SBP) was measured by telemetry. Metabolic parameters were measured weekly, and tissue samples were harvested after two weeks of treatment. None of the administered chymase inhibitors affected the development of hypertension in young rats. Only RIY exhibited beneficial properties when administered in the established phase of hypertension: SBP decreased from 165 ± 10 to 157 ± 7 mmHg while the excretion of nitric oxide metabolites increased significantly. The glomerulosclerosis index was lower after RIY treatment in both age groups (significant only in young rats 0.29 ± 0.05 vs 0.48 ± 0.04 in the control group; p &lt; 0.05). Hence, it seems that peptide RIY exhibits some positive effect on renal morphology. The results obtained suggest that the peptide RIY may be a useful tool in the treatment of hypertension, especially in cases when ACE inhibitors are not effective.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Nai-Chia Fan ◽  
Chih-Min Tsai ◽  
Chien-Ning Hsu ◽  
Li-Tung Huang ◽  
You-Lin Tain

Asymmetric dimethylarginine (ADMA) reduces nitric oxide (NO), thus causing hypertension. ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH), which can be inhibited by oxidative stress. N-Acetylcysteine (NAC), an antioxidant, can facilitate glutathione (GSH) synthesis. We aimed to determine whether NAC can prevent hypertension by regulating the ADMA-DDAH pathway in spontaneously hypertensive rats (SHR). Rats aged 4 weeks were assigned into 3 groups (n=8/group): control Wistar Kyoto rats (WKY), SHR, and SHR receiving 2% NAC in drinking water. All rats were sacrificed at 12 weeks of age. SHR had higher blood pressure than WKY, whereas NAC-treated animals did not. SHR had elevated plasma ADMA levels, which was prevented by NAC therapy. SHR had lower renal DDAH activity than WKY, whereas NAC-treated animals did not. Renal superoxide production was higher in SHR than in WKY, whereas NAC therapy prevented it. NAC therapy was also associated with higher GSH-to-oxidized GSH ratio in SHR kidneys. Moreover, NAC reduced oxidative stress damage in SHR. The observed antihypertensive effects of NAC in young SHR might be due to restoration of DDAH activity to reduce ADMA, leading to attenuation of oxidative stress. Our findings highlight the impact of NAC on the development of hypertension by regulating ADMA-DDAH pathway.


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