Altered Cardiac β-adrenoreceptors in Spontaneously Hypertensive Rats Receiving Salt Excess

1980 ◽  
Vol 59 (s6) ◽  
pp. 169s-170s ◽  
Author(s):  
A. A. MacPhee ◽  
H. L. Blakesley ◽  
Karen A. Graci ◽  
E. D. Frohlich ◽  
F. E. Cole

1. Altered adrenergic responsiveness of hearts and blood vessels occurs in both experimental and clinical hypertension. 2. Since salt excess aggravates both types of hypertension, we investigated β-adrenoreceptor properties in the hearts of spontaneously hypertensive and normotensive rats drinking 1% NaCl or tap water for 3 weeks. 3. Sodium loading increased heart weight in both spontaneously hypertensive and normotensive rats. 4. In spontaneously hypertensive rats excess salt attenuated the age-related decrease in β-adrenoreceptor number observed in spontaneously hypertensive and normotensive rats drinking tap water and in normotensive rats drinking 1% NaCl. 5. Unlike the normotensive rats, which did not show a relationship between β-adrenoreceptor number and blood pressure, spontaneously hypertensive rats on tap water and 1% NaCl showed a significant negative logarithmic relationship between these two variables. These data provide further evidence implicating sodium excess as an aggravating factor in this model of experimental hypertension.

1985 ◽  
Vol 69 (5) ◽  
pp. 511-515 ◽  
Author(s):  
P. J. O. Manhem ◽  
S. A. Clark ◽  
W. B. Brown ◽  
G. D. Murray ◽  
J. I. S. Robertson

1. Chlorothiazide (100 mg/kg body weight) was given by gavage daily to spontaneously hypertensive rats for 4 weeks. Another group of spontaneously hypertensive rats was given only tap water and served as control. 2. Measurements of total exchangeable sodium, blood pressure and weight were performed for 2 weeks before and for 4 weeks during treatment. 3. Before treatment, exchangeable sodium, blood pressure and weight were similar in the two groups of rats. 4. Chlorothiazide significantly attenuated the blood pressure increase in spontaneously hypertensive rats, the effect being most marked during the first 2 1/2 weeks of treatment and less thereafter. 5. Rats in the chlorothiazide-treated group gained weight more slowly than did those of the control group. 6. Exchangeable sodium, expressed as mmol/kg body weight, did not differ significantly between the two groups at any stage. 7. When exchangeable sodium was expressed as mmol/rat, there was a more gradual rise in the chlorothiazide-treated animals, in accordance with their slower gain in weight. 8. There was no temporal association between the antihypertensive effect of chlorothiazide and changes in exchangeable sodium. 9. Thus whereas chlorothiazide treatment of spontaneously hypertensive rats slows the increase of both weight and exchangeable sodium, other mechanisms are apparently responsible for the antihypertensive action of the drug.


2019 ◽  
Vol 317 (5) ◽  
pp. H1013-H1027 ◽  
Author(s):  
Cameron G. McCarthy ◽  
Camilla F. Wenceslau ◽  
Fabiano B. Calmasini ◽  
Nicole S. Klee ◽  
Michael W. Brands ◽  
...  

Insufficient autophagy has been proposed as a mechanism of cellular aging, as this leads to the accumulation of dysfunctional macromolecules and organelles. Premature vascular aging occurs in hypertension. In fact, many factors that contribute to the deterioration of vascular function as we age are accelerated in clinical and experimental hypertension. Previously, we have reported decreased autophagy in arteries from spontaneously hypertensive rats (SHRs); however, the effects of restoring autophagic activity on blood pressure and vascular function are currently unknown. We hypothesized that reconstitution of arterial autophagy in SHRs would decrease blood pressure and improve endothelium-dependent relaxation. We treated 14- to 18-wk-old Wistar rats ( n = 7 vehicle and n = 8 trehalose) and SHRs ( n = 7/group) with autophagy activator trehalose (2% in drinking water) for 28 days. Blood pressure was measured by radiotelemetry, and vascular function and structure were measured in isolated mesenteric resistance arteries (MRAs) using wire and pressure myographs, respectively. Treatment with trehalose had no effect on blood pressure in SHRs; however, isolated MRAs presented enhanced relaxation to acetylcholine, in a cyclooxygenase- and reactive oxygen species-dependent manner. Similarly, trehalose treatment shifted the relaxation to the Rho kinase (ROCK) inhibitor Y-27632 to the right, indicating reduced ROCK activity. Finally, trehalose treatment decreased arterial stiffness as indicated by the slope of the stress-strain curve. Overall these data indicate that reconstitution of arterial autophagy in SHRs improves endothelial and vascular smooth muscle function, which could synergize to prevent stiffening. As a result, restoration of autophagic activity could be a novel therapeutic for premature vascular aging in hypertension. NEW & NOTEWORTHY This work supports the concept that diminished arterial autophagy contributes to premature vascular aging in hypertension and that therapeutic reconstitution of autophagic activity can ameliorate this phenotype. As vascular age is a new clinically used index for cardiovascular risk, understanding this mechanism may assist in the development of new drugs to prevent premature vascular aging in hypertension. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/behind-the-bench-episode-one-cam-squared/ .


Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3758 ◽  
Author(s):  
Paola Marcolongo ◽  
Alessandra Gamberucci ◽  
Gabriella Tamasi ◽  
Alessio Pardini ◽  
Claudia Bonechi ◽  
...  

Blood pressure control in hypertensive subjects calls for changes in lifestyle, especially diet. Tomato is widely consumed and rich in healthy components (i.e., carotenoids, vitamins and polyphenols). The aim of this study was to evaluate the chemical composition and antihypertensive effects of locular gel reconstituted in serum of green tomatoes of “Camone” variety. Tomato serum and locular gel were chemically characterised. The antihypertensive effects of the locular gel in serum, pure tomatine, and captopril, administered by oral gavage, were investigated for 4 weeks in male spontaneously hypertensive and normotensive rats. Systolic blood pressure and heart rate were monitored using the tail cuff method. Body and heart weight, serum glucose, triglycerides and inflammatory cytokines, aorta thickness and liver metabolising activity were also assessed. Locular gel and serum showed good tomatine and polyphenols content. Significant reductions in blood pressure and heart rate, as well as in inflammatory blood cytokines and aorta thickness, were observed in spontaneously hypertensive rats treated both with locular gel in serum and captopril. No significant effects were observed in normotensive rats. Green tomatoes locular gel and serum, usually discarded during tomato industrial processing, are rich in bioactive compounds (i.e., chlorogenic acid, caffeic acid and rutin, as well as the glycoalkaloids, α-tomatine and dehydrotomatine) that can lower in vivo blood pressure towards healthier values, as observed in spontaneously hypertensive rats.


2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Gisele Zapata-Sudo ◽  
Tais N Frazão ◽  
Jaqueline S da Silva ◽  
Eliezer J Barreiro ◽  
Carlos A Fraga ◽  
...  

Introduction: This work investigated the cardioprotective actions of the combination of a positive inotropic agent (LASSBio-294 ) and a potent vasodilator (LASSBio-897) in spontaneously hypertensive rats (SHR) submitted to myocardial infarction (MI). Methods: Twenty four SHR (180-200 g) were randomly divided in sham-operated (SO) and infarcted groups (MI) and each group subdivided in two: treatment with vehicle (DMSO) or with LASSBio-294 + LASSBio-897 (5mg/kg each, p.o.) during 8 weeks. After treatment period, the animals were submitted to echocardiography to determine the anterior wall thickness (AWT), ejection fraction (EF), fractional shortening (FS) and the ratio of early and late transmitral filling velocity (E/A). In addition, the following hemodynamic parameters were evaluated: mean blood pressure (MBP), left ventricular end diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVESP) and LV contractility and relaxation (dp/dt max ). Hypertrophy was measured using the relation between heart weight to body weight (HW/BW). The volume fraction of collagen (%) was determined by measuring the area of H&E stained tissue within a given field. Results: MI induced in SHR promoted a decrease in AWT; EF; FS and E/A from 2.0 ± 0.4 to 1.6 ± 0.9 mm; from 53.1 ± 7.5 to 25.3 ± 6.4 %; from 40.0 ± 0.9 to 25.3 ± 11.0 %; and from 1.4 ± 0.1 to 0.9 ± 0.1, respectively. Treatment with the combination of drugs, increased AWT to 2.5 ± 0.6 mm; EF to 73.2 ± 1.0 %; FS to 43.5 ± 6.6%; and E/A to 1.3 ± 0.1. Increase of LVEDP from 4.6 ± 0.3 to 30.0 ± 3.6 mmHg and duplicated oxygen consumption were observed in MI-SHR. The negative dP/dt was reduced from 6152 ± 1015 to 3957 ± 1225 mm Hg/s. After treatment, all hemodynamic parameters were restored to values similar to SO group. Mean blood pressure which was increased after MI from 168. 2 ± 18.6 to 197.7 ± 10.7 returned to 137.0 ± 19.3 mm Hg after treatment. Increased deposition of colagen from 15.1 ± 3.9 to 24.0 ± 0.9 % induced by MI was prevented with treatment with the combination of drugs (12.9 ± 3.8 %). Conclusion: Oral administration of the combination of LASSBio-294 and LASSBio-897 could be considered promising in preventing cardiac dysfunction in SHR submitted to MI.


1995 ◽  
Vol 89 (3) ◽  
pp. 255-260 ◽  
Author(s):  
Masanori Iwase ◽  
Miya Wada ◽  
Masanori Wakisaka ◽  
Hideyuki Yoshizumi ◽  
Mototaka Yoshinari ◽  
...  

1. We studied the effects of maternal diabetes on blood pressure and glucose tolerance in the adult female offspring of spontaneously hypertensive rats. 2. Female spontaneously hypertensive rats were rendered diabetic by neonatal streptozotocin treatment, and then were mated with untreated male spontaneously hypertensive rats. Moderately severe hyperglycaemia was maintained during the gestation. 3. The birth weight was significantly lower in the female offspring of the diabetic dams than in the female offspring of the non-diabetic dams. The systolic blood pressure was significantly higher in the offspring from the diabetic dams than that from the control dams at 6 months of age (192 ± 4 mmHg versus 213 ± 4 mmHg, P < 0.01). The heart weight was also significantly increased in the offspring of the diabetic dams. Both the blood pressure and heart weight were inversely related to the birth weight. On the other hand, glucose tolerance was unaffected by maternal diabetes. 4. Maternal diabetes aggravated the severity of hypertension in the adult female offspring of spontaneously hypertensive rats. This suggests the importance of the metabolic environment during fetal growth for the development of hypertension.


2013 ◽  
pp. 237-245 ◽  
Author(s):  
S. ALBARWANI ◽  
S. AL-SIYABI ◽  
M. O. TANIRA

The aim of this work was to investigate the effect of 10 weeks of lisinopril treatment to spontaneously hypertensive rats (SHRs) on day/night variations of blood pressure, heart rate and autonomic cardio-regulation parameters. Male SHR with surgically implanted radio-telemetry implant that provided direct measurements of arterial pressure and electrocardiogram wave were used. Animals were allocated to two groups (n=5 each). The first group was treated with lisinopril (20 mg/kg by gavage) daily for 10 weeks (treated group); whereas the second was gavaged daily with tap water (untreated group). Arterial blood pressure, ECG and other telemetry parameters were recorded at the start and at the end of 10-week treatment. Collected data were analyzed using specialized software and were statistically tested. In addition to the expected lowering of blood pressure, spectral analysis of R-R intervals revealed that lisinopril treatment for 10 weeks significantly caused 2-3 fold increase in heart rate variability (HRV) during both active and inactive periods. However, R-R interval durations demonstrated variable distribution patterns during those periods. The cause of observed distribution pattern of R-R intervals during active and inactive periods may be of significance to better understand HRV changes and warrants further investigations.


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