Estrogen attenuation of the development of hypertension in spontaneously hypertensive rats

To examine the effects of estrogen on the development of high blood pressure in rats with a genetic predisposition toward hypertension, we administered to rats of the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) strains 0.05 mg mestranol daily from ages 4 to 13 wks. Control animals of each strain received corn oil placebos. Systolic blood pressure was measured by a microphonic tail-cuff technique twice a week after the rats were 6 wks of age. Estrogen treatment in SHR was associated with a significant reduction in the level of hypertension attained, but estrogen treatment had no effect on blood pressure in WKY. Estrogen prevented normal growth in SHR and WKY, but this effect (reproduced in another group of SHR and WKY by restriction of food intake) was not related to the lower blood pressures seen in estrogen-treated SHR. Thus, it appeared that estrogen administration attenuated the rise in blood pressure normally seen in SHR and that this attenuation was independent of the estrogenic effect on body weight.

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Cell Membrane Microviscosity and Ca2+-Mg2+-ATPase Activity do Not Contribute to Hypertension in the Spontaneously Hypertensive Rat Model

Clinical Science ◽

10.1042/cs0850585 ◽

1993 ◽

Vol 85 (5) ◽

pp. 585-591 ◽

Cited By ~ 3

Author(s):

Robert I Norman ◽

Navtej Achall

Keyword(s):

Blood Pressure ◽

Atpase Activity ◽

Spontaneously Hypertensive Rats ◽

Spontaneously Hypertensive Rat ◽

Hypertensive Rats ◽

Membrane Microviscosity ◽

Spontaneously Hypertensive ◽

Blood Pressures ◽

Wistar Kyoto ◽

Spontaneously Hypertensive Rat Model

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.

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Heme oxygenase substrates acutely lower blood pressure in hypertensive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.3.h1132 ◽

1996 ◽

Vol 271 (3) ◽

pp. H1132-H1138 ◽

Cited By ~ 26

Author(s):

R. A. Johnson ◽

M. Lavesa ◽

K. DeSeyn ◽

M. J. Scholer ◽

A. Nasjletti

Keyword(s):

Blood Pressure ◽

Carbon Monoxide ◽

Heme Oxygenase ◽

Lower Blood Pressure ◽

Sprague Dawley ◽

Hypertensive Rats ◽

Free Iron ◽

Spontaneously Hypertensive ◽

Lower Blood ◽

Wistar Kyoto

Heme oxygenase catalyzes the metabolism of heme to biliverdine, free iron, and carbon monoxide. The current study was designed to determine if treatment with the heme oxygenase substrates heme-L-arginate or heme-L-lysinate, to stimulate formation of heme oxygenase products, can lower blood pressure in the rat. Heme-L-arginate (45 mumol/kg ip) and heme-L-lysinate (45 mumol/kg ip) acutely lowered blood pressure in awake spontaneously hypertensive rats (SHR) by approximately 35 mmHg. For both heme oxygenase substrates, this effect was blunted by pretreatment with an inhibitor of heme oxygenase, zinc deuteroporphyrin 2,4-bis glycol. Heme-L-lysinate also lowered arterial pressure in deoxycorticosterone acetate-salt hypertensive rats and in rats with phenylephrine-induced hypertension, indicating that the vasodepressive actions of heme may be extended to other hypertensive models. However, neither heme-L-arginate nor heme-L-lysinate decreased blood pressure in normotensive controls. The heme oxygenase product biliverdine did not lower blood pressure in SHR, and the vasodepressive actions of heme-L-lysinate were unaffected by pretreatment with deferoxamine to chelate free iron. Carbon monoxide (12 ml/kg ip) lowered blood pressure in SHR and in rats made hypertensive by phenylephrine infusion, had no effect on blood pressure in Wistar-Kyoto rats, and elicited only a modest vasodepressive response in normotensive Sprague-Dawley rats. We conclude that heme-bearing preparations can lower blood pressure in hypertensive rats, presumably via heme oxygenase-mediated formation of carbon monoxide.

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PET-CT and RNA sequencing reveal novel targets for acupuncture-induced lowering of blood pressure in spontaneously hypertensive rats

Scientific Reports ◽

10.1038/s41598-021-90467-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jing Li ◽

Chong Peng ◽

Dongjian Lai ◽

Yajing Fang ◽

Daihong Luo ◽

...

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Negative Control ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Pet Ct ◽

Lower Blood ◽

Mrna And Protein Expression ◽

Wistar Kyoto ◽

Control Sham

AbstractManual acupuncture (MA) can be used to manage high blood pressure; however, the underlying molecular mechanism remains unknown. To explore the mechanism of acupuncture in the treatment of hypertension, Wistar Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) were subjected to either MA stimulation or the corresponding sham procedure as a negative control (Sham-MA) for 1 week. PET-CT scans, transcriptomics and molecular biology were used to evaluate the effect of MA. The results show that MA can regulate blood pressure in SHRs, change the glucose metabolism of the paraventricular hypothalamus (PVH), and affect the mRNA and protein expression levels of differentially expressed genes in the PVH. These genes may lower blood pressure by regulating angiotensin, endothelial function and inflammation. These findings reveal that MA regulates multiple biological processes and genes/proteins of the PVH, and provide a solid theoretical basis for exploring the mechanisms by which MA regulates hypertension.

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Effects of dietary Ca2+ on erythrocyte Na+-transport systems in spontaneously hypertensive rats

Clinical Science ◽

10.1042/cs0810107 ◽

1991 ◽

Vol 81 (1) ◽

pp. 107-112 ◽

Cited By ~ 5

Author(s):

K. Fujito ◽

M. Yokomatsu ◽

N. Ishiguro ◽

H. Numahata ◽

Y. Tomino ◽

...

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Transport Systems ◽

Hypertensive Rats ◽

Na Transport ◽

Spontaneously Hypertensive ◽

Na Pump ◽

Wistar Kyoto ◽

Increased Activity ◽

Regulation Of Blood Pressure

1. The purpose of this study was to determine the effect of dietary Ca2+ intake on blood pressure and erythrocyte Na+ transport in spontaneously hypertensive rats. 2. Spontaneously hypertensive rats and Wistar-Kyoto rats were fed diets with three different Ca2+ contents, 0.1% (low-Ca2+ diet), 0.6% (normal-Ca2+ diet) and 4.0% (high-Ca2+ diet), between 6 and 20 weeks of age. At 20 weeks of age, the levels of erythrocyte Na+ efflux, as well as Na+ and K+ contents in erythrocytes, were measured. 3. On the low-Ca2+ diet, spontaneously hypertensive rats showed an enhancement of hypertension. Conversely, on the high-Ca2+ diet, they showed an attenuation of the increase in blood pressure. Spontaneously hypertensive rats had a lower erythrocyte Na+ content and increased activity of the Na+ pump at higher levels of dietary Ca2+. Passive Na+ permeability and Na+-K+ co-transport were similar in spontaneously hypertensive rats on the low-, normal- and high-Ca2+ diets. There were no significant differences in blood pressure and in Na+ pump activity in WKY on the three different diets. 4. It is concluded that dietary Ca2+ might affect the regulation of blood pressure in spontaneously hypertensive rats by changing the activity of Na+ pump in the cell membrane.

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Increased Pressor Responsiveness to Enkephalin in Spontaneously Hypertensive Rats: The Role of Vasopressin

Clinical Science ◽

10.1042/cs059235s ◽

1980 ◽

Vol 59 (s6) ◽

pp. 235s-237s ◽

Cited By ~ 17

Author(s):

R. W. Rockhold ◽

J. T. Crofton ◽

L. Share

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Pressor Response ◽

Cardiovascular Effects ◽

Hypertensive Rats ◽

Methionine Enkephalin ◽

Spontaneously Hypertensive ◽

Wistar Kyoto Rats ◽

Wistar Kyoto

1. The cardiovascular effects of an enkephalin analogue were examined in spontaneously hypertensive and normotensive Wistar-Kyoto rats. (D-Ala2)-methionine enkephalin caused a biphasic increase in blood pressure and an increase in heart rate after intracerebroventricular injection. 2. The initial pressor response to (D-Ala2)-methionine enkephalin was greater in hypertensive than in normotensive rats. No difference was noted between groups during the secondary pressor response. Heart rate increases paralleled the secondary increase in blood pressure. 3. Naloxone pretreatment abolished the secondary increase in blood pressure and the tachycardia, but did not blunt the initial pressor response in female Wistar-Kyoto rats. 4. Plasma levels of arginine vasopressin were depressed during the plateau phase of the pressor response in hypertensive rats given intracerebroventricular (d-Ala2)-methionine enkephalin. 5. The results suggest that the cardiovascular effects of central enkephalin are not due to vasopressin, but may involve activation of the sympathetic nervous system.

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Metformin decreases plasma insulin levels and systolic blood pressure in spontaneously hypertensive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.267.4.h1250 ◽

1994 ◽

Vol 267 (4) ◽

pp. H1250-H1253 ◽

Cited By ~ 5

Author(s):

S. Verma ◽

S. Bhanot ◽

J. H. McNeill

Keyword(s):

Blood Pressure ◽

Systolic Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Plasma Insulin ◽

Metformin Treatment ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Insulin Levels ◽

Plasma Insulin Levels ◽

Wistar Kyoto

To determine the relationship between hyperinsulinemia and hypertension in spontaneously hypertensive rats (SHR), the antihyperglycemic agent metformin was administered to SHR and their Wistar-Kyoto (WKY) controls, and its effects on plasma insulin levels and blood pressure were examined. Five-week-old rats were started on oral metformin treatment (350 mg.kg-1.day-1, which was gradually increased to 500 mg.kg-1.day-1 over a 2-wk period). Metformin treatment caused sustained decreases in plasma insulin levels in the SHR (27.1 +/- 2.3 vs. untreated SHR 53.5 +/- 2.7 microU/ml, P < 0.001) without having any effect in the WKY (30.7 +/- 2.2 vs. untreated WKY 37.8 +/- 1.6 microU/ml, P > 0.05). The treatment did not affect the plasma glucose levels in any group. Metformin treatment also attenuated the increase in systolic blood pressure in the SHR (157 +/- 6.0 vs. untreated SHR 196 +/- 9.0 mmHg, P < 0.001) but had no effect in the WKY (134 +/- 3 vs. untreated WKY 136 +/- 4 mmHg, P > 0.05). Furthermore, raising plasma insulin levels in the metformin-treated SHR to levels that existed in the untreated SHR reversed the effect of metformin on blood pressure (189 +/- 3 vs. untreated SHR 208 +/- 5.0 mmHg, P > 0.05). These findings suggest that either hyperinsulinemia may contribute toward the increase in blood pressure in the SHR or that the underlying mechanism is closely associated with the expression of both these disorders.

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Contribution of Vascular Nitric Oxide to Basal Blood Pressure in Conscious Spontaneously Hypertensive Rats and Normotensive Wistar Kyoto Rats

Clinical Science ◽

10.1042/cs0890177 ◽

1995 ◽

Vol 89 (2) ◽

pp. 177-182 ◽

Cited By ~ 31

Author(s):

Naoyoshi Minami ◽

Yutaka Imai ◽

Jun-Ichiro Hashimoto ◽

Keishi Abe

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Mean Arterial Pressure ◽

Methyl Ester ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Wistar Kyoto Rats ◽

Basal Blood Pressure ◽

Wistar Kyoto

1. The aim of this study was to clarify the extent to which vascular nitric oxide contributes to basal blood pressure in conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. 2. The contribution of vascular nitric oxide to maintenance of blood pressure was estimated by measuring the pressor response to an intravenous injection of nitric oxide synthase inhibitor, Nω-l-arginine methyl ester, given after serial injections of captopril, vasopressin V1-receptor antagonist (V1-antagonist) and ganglion blocker (pentolinium) in conscious spontaneously hypertensive and Wistar Kyoto rats aged 20–28 weeks. To estimate the ‘amplifier property’ of hypertrophied vasculature in spontaneously hypertensive rats, which is known to modulate pressor responses, the lower blood pressure plateau after serial injections of captopril, V1-antagonist and pentolinium and the maximum blood pressure elicited by subsequent injection of increasing doses of phenylephrine were also measured. 3. The serial injections of captopril, V1-antagonist and pentolinium decreased mean arterial pressure from 164 ± 9 mmHg to 67 ± 2 mmHg and from 117 ± 2 mmHg to 49 ± 1 mmHg in spontaneously hypertensive and Wistar Kyoto rats respectively. The subsequent injection of Nω-l-arginine methyl ester restored mean arterial pressure almost to its control levels in both spontaneously hypertensive and Wistar Kyoto rats. The absolute changes in mean arterial pressure elicited by Nω-l-arginine methyl ester were significantly greater in spontaneously hypertensive than in Wistar Kyoto rats (P < 0.01), but there was no significant difference in the responses to Nω-l-arginine methyl ester when they were expressed as percentages of either the lower blood pressure plateau or maximum blood pressure. 4. These results indicate that basal blood pressure in both spontaneous hypertensive and Wistar Kyoto rats is maintained by a balance between vascular nitric oxide and major pressor systems. They also suggest that the vasodilatory effect of vascular nitric oxide does not differ between spontaneously hypertensive and Wistar Kyoto rats, and that the increased pressor effect of Nω-l-arginine methyl ester in spontaneously hypertensive rats is due to a vascular amplifier mechanism.

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Ca2+ sensitization and Ca2+ entry in the control of blood pressure and adrenergic vasoconstriction in conscious Wistar–Kyoto and spontaneously hypertensive rats

Journal of Hypertension ◽

10.1097/hjh.0b013e328362adb3 ◽

2013 ◽

Vol 31 (10) ◽

pp. 2025-2035 ◽

Cited By ~ 14

Author(s):

Michal Behuliak ◽

Mária Pintérová ◽

Michal Bencze ◽

Miriam Petrová ◽

Silvia Líšková ◽

...

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Wistar Kyoto

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Hypertension transmitted by kidneys from stroke-prone spontaneously hypertensive rats

AJP Renal Physiology ◽

10.1152/ajprenal.1989.257.2.f197 ◽

1989 ◽

Vol 257 (2) ◽

pp. F197-F203 ◽

Cited By ~ 4

Author(s):

R. Rettig ◽

H. Stauss ◽

C. Folberth ◽

D. Ganten ◽

B. Waldherr ◽

...

Keyword(s):

Blood Pressure ◽

Renal Transplantation ◽

Spontaneously Hypertensive Rats ◽

Plasma Renin ◽

F1 Hybrids ◽

Hypertensive Rats ◽

Plasma Urea ◽

Spontaneously Hypertensive ◽

Major Function ◽

Wistar Kyoto

We determined whether transplantations of kidneys from stroke-prone spontaneously hypertensive rats (SPSHR) and from normotensive Wistar-Kyoto rats (WKY) alter blood pressure in renal graft recipients. Kidneys taken from seven male SPSHR and seven male WKY rats (blood pressure 186 +/- 4.8 and 111 +/- 3.7 mmHg, respectively) at the age of 20 wk were transplanted, using microsurgical techniques, to bilaterally nephrectomized age-matched male F1 hybrids (blood pressure 136 +/- 2.6 and 138 +/- 6.3 mmHg, respectively) bred from SPSHR and WKY parents. After renal transplantation, blood pressure in recipients of SPSHR kidneys rose to 146 +/- 11.8 (week 2), 163 +/- 16.4 (week 3), 192 +/- 17.1 (week 4), 222 +/- 17.7 (week 5), 221 +/- 12.6 (week 6), 218 +/- 20.3 (week 7), and 239 +/- 9.2 mmHg (week 8). There was no significant change in blood pressure in recipients of WKY kidneys. All rats recovered rapidly from surgery. After renal transplantation, there was a significant increase in daily water intake, a decrease in plasma renin activity, and a slight rise in plasma urea concentration. Our data show that transplantation of kidneys from adult SPSHR causes hypertension in normotensive recipients, indicating a major function for the kidney in SPSHR hypertension.

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