Central effects of mineralocorticoid antagonist RU-28318 on blood pressure of DOCA-salt hypertensive rats

1994 ◽  
Vol 267 (6) ◽  
pp. E927-E933 ◽  
Author(s):  
D. T. Van den Berg ◽  
E. R. de Kloet ◽  
W. de Jong

The role of brain mineralocorticoid receptor (MR) sites in the pathogenesis of mineralocorticoid hypertension was studied after an intracerebroventricular injection of the MR antagonist RU-28318. Male Wistar rats received subcutaneously implanted deoxycorticosterone acetate (DOCA) pellets and were maintained on 0.9% saline as drinking solution. Under these conditions hypertension developed in approximately 5 wk as assessed in conscious rats by means of the tail-cuff technique. During the development of this hypertension (after 3 wk of DOCA-salt treatment) a single intracerebroventricular injection of the specific MR antagonist RU-28318 reduced systolic blood pressure (SBP) as measured with the tail-cuff method. A decrease in SBP was observed 2–24 h after this intracerebroventricular injection, with the lowest SBP values occurring at 8 h. In these animals (3 wk after DOCA implantation) continuous direct blood pressure recording via chronic cannulation revealed, on the day of the intracerebroventricular injection of RU-28318, a slight increase in arterial pressure during the light phase, followed by a decrease during the dark phase. In the established hypertensive rats (5 wk after DOCA RU-28318 on the arterial pressure or heart rate was detectable. It is concluded that central MR blockade during the development of the DOCA-salt hypertension reduces blood pressure within 24 h assessed with 1) the indirect method at certain time points after exposure to warming and stress and 2) the direct method during the dark phase of the diurnal cycle.

1990 ◽  
Vol 8 (10) ◽  
pp. 909-911 ◽  
Author(s):  
Alberto U. Ferrari ◽  
Anna Daffonchio ◽  
Francesco Albergati ◽  
Pierpaolo Bertoli ◽  
Giuseppe Mancia

1983 ◽  
Vol 245 (6) ◽  
pp. F755-F762 ◽  
Author(s):  
B. M. Iversen ◽  
L. Morkrid ◽  
J. Ofstad

The afferent arteriolar diameter (dAA) was investigated during development of hypertensive renal disease in normal and uninephrectomized control rats, in chronic DOCA-salt (DOCA), post-DOCA (p-DOCA), and chronic two-kidney one-clip (2K-1C) hypertensive rats, and in post-two-kidney one-clip (p-2K-1C) normotensive rats. dAA was measured by the microsphere method. Nephron loss was present in the kidneys exposed to elevate blood pressure. The dAA was reduced from 19.9 to 17.2 micron in the DOCA group (P less than 0.001) and from 19.1 to 16.3 micron in the nonclipped kidneys in the 2K-1C group (P less than 0.001). The dAA increased from 19.9 to 20.7 micron in the p-DOCA group. Afferent arteriolar dilatation from 19.1 to 21.0 micron (P less than 0.001) was present about 50 days after clipping in the 2K-1C group; in the clipped kidneys the dAA returned to normal (18.9 micron) after declipping. No relation between the dAA and plasma renin concentration was observed. In all models dAA was the same in three cortical layers of equal thickness. Accordingly, chronic renal DOCA-salt hypertension constricts the afferent arteriole with angiotensin-independent mechanisms. Autoregulatory dilatation of the afferent arteriole seems to be maintained for at least 50 days. When the hypertension is moderate, dAA in damaged kidneys may be dilated.


2021 ◽  
pp. 1-8
Author(s):  
Yi-Tse Hsiao ◽  
Yun-Wen Peng ◽  
Pin Huan Yu

Monitoring blood pressure helps a clinical veterinarian assess various conditions in birds. Blood pressure is not only a bio-indicator of renal or cardiovascular disease but is also a vital indicator for anesthesia. Anesthetic- and sedation-related mortality is higher in birds than dogs or cats. The traditional method of blood pressure measurement in mammals mainly relies on indirect methods. However, indirect blood pressure measurement is not reliable in birds, making the direct method the only gold standard. Although an arterial catheter can provide continuous real-time arterial pressure in birds, the method requires technical skill and is limited by bird size, and is thus not practical in birds with circulatory collapse. Intra-osseous (IO) blood pressure is potentially related to arterial pressure and may be a much easier and safer technique that is less limited by animal size. However, the relationship between IO pressure and arterial blood pressure has not been established. This study used mathematical methods to determine the relationship between IO pressure and arterial blood pressure. The Granger causality (G.C.) theory was applied in the study and used to analyze which pressure signal was leading the other. Our findings suggest that IO pressure is G.C. by arterial blood pressure; thus, the use of IO pressure measurements as an alternative to arterial blood pressure measurement is a rational approach.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Tomomi Nagayama ◽  
Yoshitaka Hirooka ◽  
Akiko Chishaki ◽  
Masao Takemoto ◽  
Yasushi Mukai ◽  
...  

Objective.Many previous clinical studies have suggested that atrial fibrillation (AF) is closely associated with hypertension. However, the benefits of antihypertensive therapy on AF are still inconsistent, and it is necessary to explore the factors augmenting AF in hypertensive rats. The aim of the present study was to investigate the correlation between arterial pressure or voltage stimulus and to the duration of electrically induced AF in normotensive or hypertensive rats.Methods.AF was reproducibly induced by transesophageal atrial burst pacing in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We did the burst pacing at high (20 V) or low (5 V) voltage.Results.Duration of AF did not correlate with systolic blood pressure (SBP) and stimulus voltage in WKY. However, only in SHR, duration of AF with high stimulus voltage significantly correlated with SBP and was significantly longer in high than in low voltage stimulus.Discussion and Conclusion.Duration of AF is augmented by high voltage stimulus with higher blood pressure in SHR.


1999 ◽  
Vol 276 (3) ◽  
pp. H944-H952 ◽  
Author(s):  
Stephanie W. Watts ◽  
Gregory D. Fink

We previously demonstrated a change in the receptors mediating 5-hydroxytryptamine (5-HT)-induced contraction in arteries of deoxycorticosterone acetate (DOCA)-salt-hypertensive rats. Specifically, contraction to 5-HT is mediated primarily by 5-HT2A receptors in arteries from normotensive sham rats and by both 5-HT2A and 5-HT2B receptors in arteries from hypertensive rats. We hypothesized that the 5-HT2B receptor may play a role in maintaining the high blood pressure of DOCA-salt-hypertensive rats, and herein we provide data connecting in vitro and in vivo findings. The endothelium-denuded isolated superior mesenteric artery of DOCA-salt rats displayed a marked increase in maximum contraction to the newly available 5-HT2B-receptor agonist BW-723C86 compared with that of arteries from sham rats, confirming that the 5-HT2B receptor plays a greater role in 5-HT-induced contraction in arteries from DOCA-salt rats. In chronically instrumented rats, the 5-HT2B-receptor antagonist LY-272015 (0.3, 1.0, and 3.0 mg/kg iv at 30-min intervals) was given cumulatively 1 time/wk during 4 wk of continued DOCA-salt treatment. LY-272015 did not reduce blood pressure of the sham-treated rats at any time or dose. However, LY-272015 (1.0 and 3.0 mg/kg) significantly reduced mean blood pressure in a subgroup of week 3 (−20 mmHg) and week 4 DOCA-salt (−40 mmHg) rats that had extremely high blood pressure (mean arterial blood pressure ∼200 mmHg). Blockade of 5-HT2Breceptors by in vivo administration of LY-272015 (3.0 mg/kg) was verified by observing reduced 5-HT-induced contraction in rat stomach fundus, the tissue from which the 5-HT2B receptor was originally cloned. These data support the novel hypothesis that 5-HT2B-receptor expression is induced during the development of DOCA-salt hypertension and contributes to the maintenance of severe blood pressure elevations.


2018 ◽  
Vol 48 (4) ◽  
pp. 654-668 ◽  
Author(s):  
HadjMostefa Khelladi ◽  
Djamil Krouf ◽  
Nawal Taleb-Dida

Purpose This paper aims to study the effect of green lemon zest combined with sardine proteins in diabetic hypertensive rats (DHRs). Design/methodology/approach Male Wistar rats (n = 30) weighing 250 ± 10 g were divided into five groups. The first group consumed a diet containing 20 per cent casein (C). The other four groups are rendered diabetic by intraperitoneal injection of streptozotocin (40 mg/kg body weight), then hypertensive by subcutaneous implantation controlled time-release pellet containing ouabain (0.25 mg/pellet). One untreated group (DHR) consumed 20 per cent casein and the three other groups consumed the same diet supplemented with 2 per cent green lemon zest (DHR-lz), or with 20 per cent of sardine protein (group DHR-sp) or with the combination of both sardine proteins and green lemon zest (group DHR-sp + lz). Findings DHRs feeding on the combination of both sardine protein (sp) and lemon zest (lz) induced a significant decrease of diastolic blood pressure and heart rates values compared with DHR (p < 0.05). The HDLC values were increased by +55 per cent in DHR-sp + lz compared with DHR group. Moreover, plasma non-HDLC concentrations were decreased significantly compared to DHR, DHR-lz, DHR-sp and C groups. In DHR-sp + lzvs DHR group, TBARS values were decreased by −25 per cent in the liver. Moreover, kidney TBARS were significantly reduced by −66, −51, −65 and −67 per cent compared with C, DHR, DHR-lz and DHR-sp, respectively. Originality/value These results suggest that consumption of green lemon zest combined with sardine proteins can reduce blood pressure and tissue oxidative damage and, therefore, help to prevent cardiovascular complications in hypertensive diabetic patients.


1983 ◽  
Vol 244 (1) ◽  
pp. H97-H101 ◽  
Author(s):  
S. Sen ◽  
R. C. Tarazi

Studies of regression of myocardial hypertrophy in spontaneously hypertensive rats (SHR) suggest that the adrenergic system may play an important role in the reversal of hypertrophy. The effect of propranolol on reversal of hypertrophy, however, is still controversial. This study describes the effect of propranolol, given alone or in combination with hydralazine in different ratios for 4 wk, on blood pressure (BP), ventricular weight, and myocardial catecholamine (MC) concentrations. The data show that a certain ratio of propranolol to hydralazine (750:30) leads to moderate BP control (196-156 mmHg) without increased MC (634 vs. 552 ng/g) and moderately reduced hypertrophy. Reduction of BP alone with increased MC (hydralazine alone) or reduction of MC without BP control (propranolol alone) failed to reduce hypertrophy. A significant correlation between both ventricular weight and heart rate with MC (r = 0.6) was obtained by multiple regression analysis. This study suggests that adrenergic factors seem to play an important role in modulating structural cardiac response to variations in arterial pressure.


2012 ◽  
Vol 109 (10) ◽  
pp. 1806-1812 ◽  
Author(s):  
Nallasamy Palanisamy ◽  
Anuradha C. Venkataraman

The study evaluates the effects of genistein on blood pressure (BP) and ultrastructural changes in kidney of fructose-fed hypertensive rats. Male Wistar rats were fed a diet containing 60 % starch or 60 % fructose as the source of carbohydrate. After 15 d, rats in each dietary group were divided into two groups and were treated with either genistein (1 mg/kg per d) in dimethylsulfoxide (DMSO) or 30 % DMSO alone. BP, pressor mechanisms, protein kinase C-βII (PKC-βII) expression, endothelial NO synthase (eNOS) expression and renal ultrastructural changes were evaluated after 60 d. Fructose-fed rats displayed significant elevation in BP and heart rate. Significant increase in plasma angiotensin-converting enzyme (ACE) activity, alterations in renal lipid profile, nitrite and kallikrein activity, enhanced expression of membrane-associated PKC-βII and decreased expression of eNOS were observed in them. Histology and electron microscopic studies showed structural changes in the kidney. Genistein administration lowered BP, restored ACE, PKC-βII and eNOS expression and preserved renal ultrastructural integrity. These findings demonstrate that genistein has effects on eNOS activity in renal cells, leading to eNOS activation and NO synthesis. These effects could have been mediated by activation of PKC-βII. The observed benefits of genistein make it a promising candidate for therapy of diabetic kidney disease.


2016 ◽  
Vol 18 (1) ◽  
pp. 113-124 ◽  
Author(s):  
G.H. CUNHA ◽  
F.V. FECHINE ◽  
F.A. FROTA BEZERRA ◽  
M.O. MORAES ◽  
E.R. SILVEIRA ◽  
...  

ABSTRACT The aim of this study was to characterize components of the EOAz and its hexane (HFEOAz), chloroform (CFEOAz) and methanol (MFEOAz) fractions, and its antihypertensive effect. EOAz was extracted from leaves by hydrodistillation. Aliquot was subjected to selective desorption with silica gel column and eluted with hexane, chloroform and methanol. The components of the EOAz and fractions were analyzed by gas chromatography coupled with mass spectrometry and nuclear magnetic resonance spectroscopy of hydrogen. Experiments of vascular reactivity were performed with isolated aortic rings of male Wistar rats. Antihypertensive effect was evaluated in hypertensive rats submitted to the inhibition of synthesis of nitric oxide. Blood pressure was measured indirectly by tail plethysmography. MFEOAz showed the lowest EC50 (150.45 µg/mL), 1,8-cineole (27.81%) and terpinen-4-ol (57.35%) as main components. Single administration by nasogastric tube of EOAz, fractions and captopril significantly reduced the blood pressure of hypertensive rats, when compared to animals of the negative control group with distilled water. In conclusion, the potency of the MFEOAz was higher than that of EOAz and other fractions. The antihypertensive effect of EOAz and fractions was similar, higher than the negative control and lower than that of captopril.


1989 ◽  
Vol 256 (1) ◽  
pp. R138-R145 ◽  
Author(s):  
J. Zicha ◽  
J. Kunes ◽  
M. Lebl ◽  
I. Pohlova ◽  
J. Slaninova ◽  
...  

The role of antidiuretic and pressor effects of vasopressin (VP) in deoxycorticosterone acetate (DOCA)-salt hypertension was studied in young and adult Brattleboro rats. The antidiuretic VP action was a necessary prerequisite for the development of severe DOCA-salt hypertension. The insufficient expansion of extracellular fluid volume in DOCA-salt-treated VP-deficient (DI) rats was associated with the attenuation of their hypertensive response, although they had highly increased blood volume and extracellular sodium. Chronic [deamino]-D-arginine vasopressin supplementation that restored volume and distribution of body fluids in DI rats permitted the full development of DOCA-salt hypertension. Blood pressure response to DOCA-salt treatment was always greater in young than in adult Brattleboro rats (even in animals lacking pressor or both VP effects). In animals in which antidiuretic VP effects were present, the pattern of body fluid response to DOCA-salt treatment was also age dependent. There was a tendency to intravascular expansion in young hypertensive rats, whereas an increase of interstitial fluid volume was found in adult animals. The elimination of VP pressor action lowered systemic resistance much more in adult than in young hypertensive rats. We conclude that 1) in adult but not in young rats antidiuretic VP effects are essential for the occurrence of blood pressure response to DOCA-salt treatment, 2) the restoration of body fluids due to antidiuretic VP action enables the development of hypertension in both age groups of DI rats, and 3) pressor VP effects contribute to the maintenance of hypertension, especially in adult animals.


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