Upregulation of endothelin-1 binding in tissues of salt-loaded stroke-prone spontaneously hypertensive rats

2002 ◽  
Vol 80 (5) ◽  
pp. 470-474 ◽  
Author(s):  
Paula Savage ◽  
Arco Y Jeng

Upon maintained on a 1% NaCl drinking solution beginning at 7 weeks of age, the stroke-prone spontaneously hypertensive rat (SHRsp) developed severe hypertension and stroke; most died by 16 weeks. The mechanism by which these diseases evolve remains unclear. Endothelin-1 (ET-1) is a potent, peptidic vasoconstrictor and is implicated in the pathogenesis of various cardiovascular, renal, and central nervous system diseases. The purpose of the present study was to compare the binding of [125I]ET-1 to the brain, heart, kidney, liver, and spleen membrane preparations of 16-week-old SHRsp and age-matched normotensive Wistar–Kyoto rats (WKY). The KD values for [125I]ET-1 binding to the corresponding tissues of the two strains were not significantly different, except in the brain (SHRsp: 17 ± 1 pM; WKY: 24 ± 1 pM). In contrast, the Bmax values measured in the brain, heart, kidney, and liver of SHRsp were 1.5- to 2.1-fold greater than those of their WKY counterparts. Competition of [125I]ET-1 binding to the membrane preparations by the specific ETA receptor antagonist BQ-123 or the specific ETB receptor agonist sarafotoxin S6c revealed a similar proportion of ETA and ETB receptor subtypes in the corresponding tissues of the two rat strains. These results indicate that ET-1 binding is upregulated in SHRsp and suggest that ET-1 may play a pathophysiological role in this animal model of genetic hypertension.Key words: ETA receptor, ETB receptor, BQ-123, sarafotoxin 6C, stroke-prone spontaneously hypertensive rats.

1985 ◽  
Vol 68 (4) ◽  
pp. 407-410 ◽  
Author(s):  
J. Higaki ◽  
T. Ogihara ◽  
Y. Kumahara ◽  
E. L. Bravo

1. Intracellular calmodulin levels were measured by direct radioimmunoassay in spontaneously hypertensive rats (SHR) and Wistar—Kyoto rats (WKY). 2. Decreased calmodulin levels were demonstrated in the brain, heart, aorta and kidney of spontaneously hypertensive rats compared with those in Wistar—Kyoto rats. 3. Calmodulin levels in the brain were also decreased in deoxycorticosterone acetate (DOCA)-salt rats, but not changed significantly in the heart, aorta and kidney compared with those in Wistar—Kyoto rats. 4. These findings suggest that intracellular calcium-dependent regulatory systems are genetically disrupted in spontaneously hypertensive rats, but this is probably not an important factor in the development of hypertension.


1978 ◽  
Vol 235 (5) ◽  
pp. F409-F416 ◽  
Author(s):  
Gerald F. DiBona ◽  
Linda L. Rios

The mechanism of exaggerated diuresis and natriuresis was studied in spontaneously hypertensive rats (SHR) by renal clearance and micropuncture techniques. Control normotensive rats of the same age and sex [Wistar-Kyoto rats (WKY)] were also studied. During the hydropenic control and the volume-expansion experimental periods absolute and fractional water and sodium excretion were greater in SHR than in WKY. Although fractional and absolute water and sodium reabsorption were similar along the proximal convolution in SHR and WKY, fractional and absolute water reabsorption in Henle's loop was less in SHR than in WKY. Hydrostatic and colloid osmotic pressures in the cortical peritubular microvasculature were similar in WKY and SHR. Acute normalization of renal perfusion pressure by aortic constriction reversed the exaggerated diuresis and natriuresis in SHR by halving the filtered load of water and sodium; whole kidney and single nephron glomerular filtration rates and blood flows decreased by 50%. It is concluded that the exaggerated diuresis and natriuresis of the spontaneously hypertensive rat is caused by a decreased reabsorption in the loop of Henle. The mechanism of this decreased reabsorption in the loop of Henle cannot be explained by alterations in the measured physical forces in the renal cortical microvasculature. natriuresis; autoregulation; volume expansion Submitted on November 15, 1977 Accepted on June 7, 1978


1981 ◽  
Vol 59 (10) ◽  
pp. 1104-1107 ◽  
Author(s):  
Thomas T. Zsotér ◽  
Steve Sirko ◽  
Camille Wolchinsky ◽  
Dezso Kadar ◽  
Laszlo Endrenyi

This study compares the uptake and release of [3H]norepinephrine and residual 3H content in the tail artery of 7- to 9-week-old and 16- to 18-week-old spontaneously hypertensive rats (SHR) and age matched normotensive Wistar Kyoto rats (WKR). The composition of the 3H overflow from the artery, analyzed with column chromatography, revealed similar proportion of norepinephrine and in metabolites, namely normetanephrine, O-methylated deaminated products, dihydroxy-phenylglycol, and dihydroxymandelic acid in SHR and WKR. [3H]Norepinephrine was retained however in greater proportion in vessels of young and older SHR than in WKR.


1995 ◽  
Vol 6 (4) ◽  
pp. 1209-1215
Author(s):  
Q C Meng ◽  
J Durand ◽  
Y F Chen ◽  
S Oparil

This study used a novel simple method for the extraction, separation, identification, and quantitation of angiotensin-like immunoactivity from tissue to examine the effects of altering dietary NaCl intake on intrarenal angiotensin I, II, and III levels in salt-sensitive, spontaneously hypertensive rats, salt-resistant Wistar-Kyoto rats, and Sprague-Dawley rats. Seven-week-old male spontaneously hypertensive rats, Wistar-Kyoto rats, and Sprague-Dawley rats were assigned randomly to a diet containing either 8% (high) or 1% (basal) salt and were maintained on these diets for 3 wk. Rats were then decapitated without prior anesthesia, and kidneys were rapidly (< 30 s) removed, snap frozen in liquid nitrogen, and stored at -80 degrees C. Frozen tissue was extracted in 2 M acetic acid and then subjected to solid-phase extraction with the cation exchange resin AG 50W X4. Angiotensin peptides were separated by reversed-phase high-performance liquid chromatography on a phenyl silica gel column with an eluent consisting of 20% acetonitrile in 0.1 M ammonium phosphate buffer, pH 4.9, and quantitated by radioimmunoassay. The elution of standard peptides under isocratic conditions revealed clear resolution of angiotensin I, II, and III and the (1-7) and (3-8) peptides. Recoveries of both labeled and unlabeled angiotensin peptide standards from the extraction step were > 90%. Renal angiotensin II stores were significantly higher in spontaneously hypertensive rats than in Wistar-Kyoto or Sprague-Dawley rats, independent of diet. Renal angiotensin II and III were further suppressed during dietary salt supplementation in both salt-resistant strains but not in the spontaneously hypertensive rat. These findings are consistent with an enhanced (compared with Wistar-Kyoto and Sprague-Dawley rats) role for angiotensin II in the kidney of the salt-sensitive, spontaneously hypertensive rat, particularly under conditions of dietary salt supplementation.


1982 ◽  
Vol 242 (4) ◽  
pp. H496-H499 ◽  
Author(s):  
W. Rascher ◽  
R. E. Lang ◽  
T. Unger ◽  
D. Ganten ◽  
F. Gross

In stroke-prone spontaneously hypertensive rats (SHRSP) and in normotensive Wistar-Kyoto rats (WKY), arginine vasopressin (AVP) was measured by means of a radioimmunoassay in the plasma, the pituitary gland, the hypothalamus, and the brain stem. In 6- and 14-wk-old SHRSP, the plasma concentration of AVP was lower than in age-matched WKY (P less than 0.01), whereas it was elevated at 28 wk of age (P less than 0.01). In the pituitary of 6-wk-old SHRSP, AVP was higher than in WKY (P less than 0.05), but no such difference was found in older rats. In the hypothalamus and the brain stem, AVP content was reduced in all age groups of SHRSP. Plasma osmolality was diminished in 28-wk-old SHRSP only (P less than 0.01), whereas hematocrit in all age groups was higher in SHRSP than in WKY. It is concluded that the secretion of AVP and possibly its synthesis in the hypothalamus are reduced in SHRSP. Whether the reduced AVP content in the brain stem is related to the sustained elevation of blood pressure has to be studied further.


Planta Medica ◽  
2020 ◽  
Vol 86 (06) ◽  
pp. 395-404 ◽  
Author(s):  
Fabiana Gomes ◽  
André M. Marques ◽  
Obadia Nathalie ◽  
Marcos Adriano Lessa ◽  
Eduardo Tibiriçá ◽  
...  

Abstract Echinodorus grandiflorus is a semiaquatic plant native to Brazil and belongs to the Alismataceae family. Infusion preparations of the leaves of this plant are often used due to its diuretic, blood pressure lowering, and anti-inflammatory properties. Our aim was to investigate the effects of chronic treatment with the crude hydroalcoholic extract of E. grandiflorus on central and peripheral microvascular changes induced in a model of hypertension and diabetes. The hemodynamic and microvascular effects of E. grandiflorus extract (50, 100, or 200 mg/kg/day for 28 days) or the isolated major diterpene from E. grandiflorus (3 to 10 mg/kg i. v.) were evaluated in spontaneously hypertensive rats using tail plethysmography and intravital fluorescence videomicroscopy, respectively, and were compared to vehicle-treated normotensive Wistar-Kyoto rats. We also investigated the protective effects of chronic treatment with E. grandiflorus (100 mg/kg/day) in brain capillary density and leukocyte-endothelium interactions on the brain vessels of DM-spontaneously (DM: diabetes mellitus) hypertensive rats. Chronically treating spontaneously hypertensive rats with increasing doses of crude hydroalcoholic E. grandiflorus extract resulted in significant dose-dependent reductions in systolic blood pressure and an anti-inflammatory effect on the brain microcirculation of DM-spontaneously hypertensive rat animals. Using laser speckle contrast imaging, we observed that intravenous administration of the major isolated clerodane diterpene metabolite (1 – 10 mg/kg) increased microvascular blood flow by 25% in spontaneously hypertensive rat skeletal muscle. The results of this study show that E. grandiflorus extracts can be useful in the prevention and reduction of microcirculatory damage in arterial hypertension and other diseases that involve microvascular dysfunction.


1977 ◽  
Vol 233 (4) ◽  
pp. H493-H499 ◽  
Author(s):  
C. J. Limas ◽  
C. Limas

Vascular prostaglandin synthesis was studied in tissues (aorta and inferior vena cava) obtained from spontaneously hypertensive rats (SHRs) of the Aoki-Okamoto strain and age-matched Wistar-Kyoto (WKYs) controls. PGE2 synthesis in aortas from SHRs was significantly enhanced at 10 wk of age (5.3 +/- 0.7 nmol PGE2/mg protein per 10 min vs. 1.9 +/- 0.03 nmol PGE2/mg protein per min in the WKYs, P less than 0.001) and increased progressively until 22 wk of age; PGE2alpha synthesis in SHRs was not significantly different from WKYs. In the venous walls from SHRs, PGF2alpha was the prostaglandin predominantly synthesized (7.1 +/- 0.6 vs. 1.9 +/- 0.05 nmol PGE2alpha/mg protein per 10 min in the WKY controls, P less than 0.01). The activities of 15-hydroxy prostaglandin dehydrogenase and PGE 9-ketoreductase were also compared in the two groups of animals. The only difference detected was a significant increase in venous PGE 9-ketoreductase of SHR's (7.3 +/- 0.06 vs. 4.8 +/- 0.04 nmol PGF2alpha/mg per min, P less than 0.01). The results suggest that increased vascular synthesis of prostaglandins accompanies the development of spontaneous hypertension and may serve to attenuate the effects of blood pressure elevation.


1987 ◽  
Vol 72 (4) ◽  
pp. 515-518 ◽  
Author(s):  
A. Berthelot ◽  
C. Luthringer ◽  
A. Exinger

1. Total plasma concentrations of bromine, copper, rubidium, selenium and zinc were measured in spontaneously hypertensive rats (SHR) and Wistar–Kyoto rats (WKY) of 5–20 weeks of age, using an X-ray fluorescence spectrometry technique. 2. Although plasma levels of bromine, rubidium, selenium and zinc varied at different ages when comparing SHR and WKY, their general evolution was similar. Copper levels increased more in SHR than in WKY. 3. These perturbations in trace element levels could perhaps participate in the establishment of hypertension in SHR, but could also be due to genetic differences between the strains, unrelated to the development of hypertension.


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.


1987 ◽  
Vol 65 (2) ◽  
pp. 230-235 ◽  
Author(s):  
C. Subah Packer ◽  
Newman L. Stephens

Prolonged isometric relaxation in hypertensive aortic and caudal arterial smooth muscle has been demonstrated; however, isobaric relaxation in resistance arteries is more pertinent to studies in hypertension. A comparative study of mesenteric arterial isobaric relaxation times was made using spontaneously hypertensive rats (SHR), normotensive Wistar–Kyoto rats (WKY), and MK-421 treated SHR (treatment commenced at 8 weeks of age and was maintained until sacrifice). Relaxation rates of vessels constricting against a range of pressures and achieving different degrees of narrowing or changes in circumference were analyzed. Comparisons were made between SHR, WKY, and MK-421 treated SHR arteries that had constricted from the same initial circumference and against the same magnitude of pressure. The SHR mesenteric arteries relaxed at a slower rate than did the WKY vessels. The normotensive MK-421 treated SHR showed the same prolonged relaxation rate as did the untreated SHR preparations. Thus the slower rate of relaxation in SHR arteries does not appear to be a consequence of the hypertension. Such prolonged time for narrowing would function to increase the average peripheral resistance and thus may contribute to the initiation and maintenance of increased blood pressure.


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