Relative Effectiveness of Chlorothiazide, Reserpine and Hydrallazine in Spontaneously Hypertensive Rats

1976 ◽  
Vol 51 (s3) ◽  
pp. 635s-637s
Author(s):  
E. D. Freis ◽  
D. O. Ragan

1. Previous studies in this laboratory indicated that a mixture of anti-hypertensive agents in the drinking water controlled the blood pressure of spontaneously hypertensive rats (SHR). The present study was designed to determine which of the agents exerted the greatest anti-hypertensive effect. 2. Treatment was begun at 12 weeks of age in groups of eleven to seventeen rats with one of the following drugs: reserpine, chlorothiazide or hydrallazine. Blood pressures were recorded by the tail method under light ether anaesthesia every 2 weeks until the rats were approximately 70 weeks of age. 3. At 50 weeks of age, blood pressure of chlorothiazaide-treated rats averaged 40 mmHg below untreated control SHR; reserpine-treated SHR were also 40 mmHg lower than control rats, and hydrallazine-treated SHR were 85 mmHg below the control rats. 4. Rats in all groups gained weight normally and appeared in good health. Although all drugs were active, hydrallazine was considerably more effective than chlorothiazide or reserpine in the SHR.

1991 ◽  
Vol 81 (3) ◽  
pp. 335-340 ◽  
Author(s):  
John S. Smeda ◽  
Olexa Tkachenko

1. Previous studies have indicated that increases in dietary K+ promote diuresis and retard stroke development in stroke-prone spontaneously hypertensive rats (spSHR) fed a Japanese-style diet containing 4% NaCl. 2. It is possible that elevations in dietary K+ retard stroke development by inducing natriuresis and facilitating the clearance of Na+, and that diuretics associated with natriuresis might also be capable of retarding stroke development in spSHR. To test if this was the case, the onset of stroke development in spSHR fed a low (0.75%) K+ diet containing 4% NaCl (controls) was monitored and compared with that in spSHR treated with (a) frusemide, (b) chlorothiazide, (c) amiloride or (d) acetazolamide, and with (e) untreated spSHR fed a high (2.11%) K+ diet. 3. The onset of stroke, as well as death resulting from stroke, occurred at a significantly later age in spSHR fed a high K+ diet than in spSHR fed a low-K+ diet, despite the fact that both groups of spSHR rats had comparable blood pressures. 4. Treatment of spSHR with the above-named diuretics before stroke development did not alter the blood pressure of the rats. The onset of stroke development and death in spSHR treated with chlorothiazide, amiloride or acetazolamide was comparable with that observed in untreated control spSHR. In spSHR treated with frusemide, the onset of stroke was comparable with that of untreated control spSHR, whereas the onset of death after stroke development was accelerated. 5. Post mortems performed on spSHR that developed stroke indicated the presence of haemorrhagic stroke of comparable severity in the six groups of spSHR studied. 6. The results indicate that treatment of spSHR with diuretics at levels which do not alter the animals’ blood pressure does not alter the timing or incidence of stroke development, and does not prolong the lifespan of the animals after stroke has developed.


1998 ◽  
Vol 76 (1) ◽  
pp. 63-67 ◽  
Author(s):  
María Reverte ◽  
Olga Flores ◽  
Belén Gallego ◽  
Antonio Lestón ◽  
José Miguel López-Novoa

We have studied during 30 days the effect of a low dose of NG-nitro-L-arginine methyl ester (1 mg ·kg-1 ·day-1 in drinking water) in the presence of D- or L-arginine (1 mg ·kg-1 ·day-1 in drinking water) in comparison with D- or L-arginine alone on blood pressure and renal function in conscious uninephrectomized female spontaneously hypertensive rats. At the end of the study, there was a significant increase in systolic blood pressure in the NG-nitro-L-arginine methyl ester + D-arginine group (307 ± 6 mmHg (1 mmHg = 133.3 Pa), n = 14, p << 0.05) in comparison with NG-nitro-L-arginine methyl ester + L-arginine (281 ± 6 mmHg, n = 14), L-arginine (262 ± 5 mmHg, n = 13), and D-arginine (258 ± 7 mmHg, n = 12) groups. There were no changes in diuresis, proteinuria, or sodium and potassium excretion between differently treated animals during this study. These results suggest that in uninephrectomized female spontaneously hypertensive rats, after 1 month blockade of NO synthesis with a low dose of NG-nitro-L-arginine methyl ester, vasculature is under tonic control by NO and it is not correlated with renal dysfunction.Key words: Key words: NG -nitro-L-arginine methyl ester (L-NAME), kidney, hypertension, spontaneously hypertensive rats, renaldysfunction, uninephrectomy.


1993 ◽  
Vol 85 (5) ◽  
pp. 585-591 ◽  
Author(s):  
Robert I Norman ◽  
Navtej Achall

1. The relationships between systolic blood pressure and altered erythrocyte Ca2+-Mg2+-ATPase activity and membrane microviscosity were assessed in membranes prepared from 20-week-old female Wistar-Kyoto normotensive and spontaneously hypertensive rats obtained from two different sources (Charles River and Harlan OLAC) and a second filial (F2) generation derived from a cross between Wistar-Kyoto rats and spontaneously hypertensive rats from one source (Charles River). 2. Spontaneously hypertensive rats from both sources had systolic blood pressures significantly higher than those of Wistar-Kyoto animals (P <0.05; 151 + 4 and 110 + 3 mmHg, Charles River; 155 + 4 and 122 + 4 mmHg, Harlan OLAC). The systolic blood pressures for the F2 rat population ranged between 73 and 168 mmHg. 3. Ca2+-Mg2+-ATPase activity was measured as ATP-dependent 45Ca2+ uptake into inside-out vesicles and microviscosity assessed by the measurement of polarization anisotropy of membrane incorporated fluorescent probes including 1,6-diphenyl-1,3,5-hexatriene, trimethylamino-1,6-diphenyl-1,3,5-hexatriene and a series of anthroyloxy fatty acids. 4. Contrary to previous studies, no relationship between adult systolic blood pressure and erythrocyte Ca2+-Mg2+-ATPase activity or general or localized membrane microviscosity was indicated by the comparison of spontaneously hypertensive and Wistar-Kyoto animals or in the analysis of the F2 rat population. 5. These results suggest that Ca2+-Mg2+-ATPase activity and membrane microviscosity are causally unrelated to hypertension in these animals. On the assumption that biophysical properties of the erythrocyte membrane reflect those of smooth muscle, our results suggest that membrane alteration does not play a significant role in the pathogenesis of hypertension in the spontaneously hypertensive rat model.


1976 ◽  
Vol 230 (5) ◽  
pp. 1354-1359 ◽  
Author(s):  
A Nagaoka ◽  
H Iwatsuka ◽  
Z Suzuoki ◽  
K Okamoto

Hypertension and stroke in spontaneously hypertensive rats (SHR) were investigated genetically using stroke-prone SHR (A3), stroke-resistant SHR (C) and their hybrids, hybrid of A3 and C (F1), offspring of F1 X F1 (F2), and those of backcrossing of F1 to the respective parental strains, BC(F1 X A3) and BC(F1 X C). The average blood pressure measured without anesthesia increased in the following order during the experimental period: C less than BC (F1 X C) less than F1 approximately F2 less than BC(F1 X A3) less than A3. The F2 represented a wider spread of variation than the F1, with some of the pressure extending into the range of both parental strains. When the drinking water was replaced with a 1% salt solution, the blood pressure increased and the onset of stroke markedly accelerated in all groups of SHR. Under the hypertensive conditions, the incidence of stroke was associated with A3-gene concentration rather than with the level of blood pressure. Similar but less dramatic effects of salt were observed in another series of hybrid groups derived from A3 and normal Wistar-Kyoto rats. These findings suggest that the genetic factors are of great importance in the development of stroke as well as hypertension in the SHR.


1986 ◽  
Vol 61 (1) ◽  
pp. 318-324 ◽  
Author(s):  
J. M. Overton ◽  
C. M. Tipton ◽  
R. D. Matthes ◽  
J. R. Leininger

To determine whether voluntary exercise would lower resting blood pressure in spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SP-SHR), two separate but interrelated investigations were undertaken. The studies were initiated when the animals were 28–35 days of age and after they were assigned to either activity or sedentary cages. The activity cages were connected to transducers and recorders that allowed the monitoring and calculation of frequency, duration, and running speed. The SHR group ran 3–7 km/day intermittently for 12 wk at high speeds (48–68 m/min), which resulted in heart rates in excess of 500 beats/min. When the SHR exercised, they seldom exceeded 33 revolutions/bout (37 m) with the majority being less than 22 revolutions/bout. This type of exercise training significantly lowered, but did not normalize, resting blood pressure by approximately 20 mmHg [nontrained (NT) = 185 +/- 5; trained (T) = 163 +/- 5 mmHg] while increasing maximum O2 consumption (VO2max) (NT = 78 +/- 2.6; T = 95 +/- 2.2 ml X min-1 X kg-1) and endurance run time (NT = 62 +/- 9.0; T = 286 +/- 15.0 min), respectively. Although SP-SHR exhibited comparable patterns of voluntary activity, the effects were not similar. First, after approximately 5 wk of consuming a special Japanese rat chow and a 1% NaCl drinking solution, cerebrovascular lesions occurred and deaths ultimately resulted in both exercising and sedentary groups. Second, although there was statistical evidence for a training effect (higher VO2max, longer VO2 test run times), voluntary exercise had no advantage in either male or female runners in lowering resting blood pressures or in improving their life-spans. Whereas voluntary activity wheel exercise or moderate forced treadmill exercise will lower resting blood pressures in young SHR populations, similar generalizations cannot be made with young SP-SHR rats.


2020 ◽  
Author(s):  
Xu-dong Zhang ◽  
Xiao-min Hao ◽  
Jing-rong Liang ◽  
Jiao-juan Wu ◽  
Yan-jun Xue ◽  
...  

Abstract Purpose: In this experiment, spontaneously hypertensive rats (SHR) were used to further explore the antihypertensive effect of acupuncture twirling reinforcing and reducing manipulation and the central effect mechanism of regulating blood pressure. Methods: 32 male SHR rats were randomly divided into 4 groups: twirling reinforcing manipulation group (RF), twirling reducing manipulation group (RD), electroacupuncture group (EA) (n = 8) and model group (M) (n = 8) and 8 WKY rats were used as blank control group (WKY). Group RD, RF and EA SHR took bilateral Taichong(LR3) point for acupuncture twirling method or electroacupuncture treatment, while WKY and M group did not use any acupuncture manipulation, but only carried out the same grasping and fixation. The differential proteins in cerebellum were screened by proteomic technology, and the key proteins and pathways involved in the pathogenesis of hypertension were selected.Results: RD, RF and EA lowered the blood pressures of the SHRs by varying degrees. The results of Parallel reaction monitoring(PRM) verification showed that among all the differential proteins, 13 differentially expressed proteins (DEPs) were selected for PRM verification. The KEGG annotations of differential proteins are involved in the regulation of lipolysis, autophagy, gap junction, phosphate inositol metabolism, splicing, lysosome, thermogenesis and RNA transport in adipocytes, etc. Conclusion: The results of the current study demonstrated that RD, RF and EA manipulations at the LR3 point reduced blood pressure and that RD was the most effective of the techniques used. Different acupuncture techniques have different pathways for screening and activating cerebellar differential proteins.


2007 ◽  
Vol 293 (4) ◽  
pp. R1573-R1579 ◽  
Author(s):  
Jennifer C. Sullivan ◽  
Laura Semprun-Prieto ◽  
Erika I. Boesen ◽  
David M. Pollock ◽  
Jennifer S. Pollock

There is a sex difference in hypertensive renal injury, with men experiencing greater severity and a more rapid progression of renal disease than women; however, the molecular mechanisms protecting against renal injury in women are unknown. The goal of this study was to determine whether sex hormones modulate blood pressure and the progression of albuminuria during the developmental phase of hypertension in male and female spontaneously hypertensive rats (SHR). Studies were also performed to examine how sex and sex hormones influence two major risk factors for albuminuria, overactivation of the renin-angiotensin system and oxidative stress. Blood pressure was measured by telemetry in gonad-intact and gonadectomized male and female SHR. Microalbumin excretion, measured over time, and macrophage infiltration were used to assess renal health. Male SHR had significantly higher blood pressures than female SHR, and gonadectomy decreased blood pressures in males with no effect in females. Male SHR displayed a gonad-sensitive increase in albuminuria over time, and female SHR had a gonad-sensitive suppression in macrophage infiltration. Female SHR had greater plasma ANG II levels and similar levels of renal cortical ANG II vs. levels shown in males but less AT1-receptor protein expression in the renal cortex. Female SHR also had a gonad-sensitive decrease in renal oxidative stress. Therefore, the renal protection afforded to female SHR is associated with lower blood pressure, decreased macrophage infiltration, and decreased levels of oxidative stress.


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