scholarly journals STIM1/Orai1 contributes to sex differences in vascular responses to calcium in spontaneously hypertensive rats

2011 ◽  
Vol 122 (5) ◽  
pp. 215-226 ◽  
Author(s):  
Fernanda R. C. Giachini ◽  
Victor V. Lima ◽  
Fernando P. Filgueira ◽  
Anne M. Dorrance ◽  
Maria Helena C. Carvalho ◽  
...  

Sex differences in Ca2+-dependent signalling and homoeostasis in the vasculature of hypertensive rats are well characterized. However, sex-related differences in SOCE (store-operated Ca2+ entry) have been minimally investigated. We hypothesized that vascular protection in females, compared with males, reflects decreased Ca2+ mobilization due to diminished activation of Orai1/STIM1 (stromal interaction molecule 1). In addition, we investigated whether ovariectomy in females affects the activation of the Orai1/STIM1 pathway. Endothelium-denuded aortic rings from male and female SHRSP (stroke-prone spontaneously hypertensive rats) and WKY (Wistar–Kyoto) rats and from OVX (ovariectomized) or sham female SHRSP and WKY rats were used to functionally evaluate Ca2+ influx-induced contractions. Compared with females, aorta from male SHRSP displayed: (i) increased contraction during the Ca2+-loading period; (ii) similar transient contraction during Ca2+ release from the intracellular stores; (iii) increased activation of STIM1 and Orai1, as shown by the blockade of STIM1 and Orai1 with neutralizing antibodies, which reversed the sex differences in contraction during the Ca2+-loading period; and (iv) increased expression of STIM1 and Orai1. Additionally, we found that aortas from OVX-SHRSP showed increased contraction during the Ca2+-loading period and increased Orai1 expression, but no changes in the SR (sarcoplasmic reticulum)-buffering capacity or STIM1 expression. These findings suggest that augmented activation of STIM1/Orai1 in aortas from male SHRSP represents a mechanism that contributes to sex-related impaired control of intracellular Ca2+ levels. Furthermore, female sex hormones may negatively modulate the STIM/Orai1 pathway, contributing to vascular protection observed in female rats.

1998 ◽  
Vol 274 (2) ◽  
pp. R510-R516 ◽  
Author(s):  
Margaret P. Chandler ◽  
Stephen E. Dicarlo

Arterial pressure (AP), heart rate (HR), cardiac sympathetic tonus (ST), and parasympathetic tonus (PT) were determined in spontaneously hypertensive rats (SHR, 8 male and 8 female) and Wistar-Kyoto normotensive rats (WKY, 8 male and 12 female) before and after acute exercise. Before exercise, hypertensive rats (regardless of gender) had an increased ST (+15 beats/min), increased resting HR (+12 beats/min), and decreased PT (−11 beats/min). Similarly, female rats (regardless of strain) also had an increased ST (+15 beats/min), increased resting HR (+39 beats/min), and decreased PT (−14 beats/min). Hypertensive rats had a significant reduction in AP (−17 ± 3 mmHg), ST (−26 beats/min), PT (−7 beats/min), and HR (−14 beats/min) after exercise. In contrast, AP was not reduced in normotensive rats and ST (+18 beats/min) and HR (+42 beats/min) were increased in female normotensive rats after exercise. However, male normotensive rats had a postexercise reduction in ST (−14 beats/min) and HR (−19 beats/min). In summary, AP, ST, and resting HR were higher whereas PT was lower in hypertensive vs. normotensive rats. Furthermore, females had a higher resting HR, intrinsic HR, and ST and lower PT than male rats. These data demonstrate that gender and the resting level of AP influence cardiac autonomic regulation.


2002 ◽  
Vol 93 (2) ◽  
pp. 479-483 ◽  
Author(s):  
Eric Kensicki ◽  
Gail Dunphy ◽  
Daniel Ely

The objective of this study was to examine whether or not estradiol (E2) alters sodium intake in hypertensive and normotensive female rats. It was hypothesized that higher doses of E2 would increase sodium consumption and that this response would be greater in spontaneously hypertensive rats (SHR) compared with Wistar Kyoto (WKY) rats. The study involved female SHR and WKY ( n = 12/group). All animals were ovariectomized. Six of twelve rats from each strain received three progressively larger doses of β-estradiol propionate (each dose lasting 2 wk), whereas the other six rats from each strain received sham implants. Blood E2 levels were measured by radioimmunoassay after each 2-wk period, allowing a 10-day washout period before the next E2 dose. Rats had access to 0.0, 0.5, 1.0, and 1.5% NaCl solutions to drink throughout the experiment. There was a significant positive correlation between sodium intake and plasma E2 ( r = 0.8, P < 0.001). Both strains avoided the 1.5% NaCl, and the increased sodium intake was achieved by an increase in consumption of the 0.5% NaCl. SHR females consumed more sodium than WKY females, which is similar to what has been observed in males of these strains. In conclusion, E2 was positively correlated with sodium intake in both strains of rat, with the hypertensive rats consuming more sodium than the normotensive rats.


1987 ◽  
Vol 65 (12) ◽  
pp. 2466-2471 ◽  
Author(s):  
G. Massicotte ◽  
J. St-Louis ◽  
A. Parent ◽  
E. L. Schiffrin

We have investigated the in vitro vascular responses to vasoconstrictor agents in pregnant normotensive (Sprague–Dawley (SDR) and Wistar–Kyoto (WKR)) and spontaneously hypertensive rats (SHR) to measure the sensitivity and contractility of blood vessels of pregnant rats. In the perfused mesenteric vascular bed from rats on the 21st day of gestation, the concentration–response curves for the increase in perfusion pressure by arginine8-vasopressin and norepinephrine were displaced to the right by comparison to nonpregnant female rats when all strains of rats were considered together. The increase in EC50 to both agents in pregnant rats was from 1.3- to 2.7-fold in the mesenteric bed; SDR showed the highest increase in EC50, followed by SHR and WKR. No consistent effect was observed on the maximum response. Similar results were obtained in isolated portal veins for angiotensin II and norepinephrine, except that the increase in EC50 in pregnant rats was smaller in magnitude (from 1.0 to 1.7) and followed the same interstrain pattern. These data show that the decreased responsiveness to vasoconstrictor agents in pregnant rats observed in vitro is similar in normotensive and hypertensive rats and suggest that the factor(s) responsible for this effect is a phenomenon affecting vascular smooth muscle in both arteries and veins.


1995 ◽  
Vol 78 (1) ◽  
pp. 101-111 ◽  
Author(s):  
J. M. Lash ◽  
H. G. Bohlen

These experiments determined whether a deficit in oxygen supply relative to demand could account for the sustained decrease in tissue PO2 observed during contractions of the spinotrapezius muscle in spontaneously hypertensive rats (SHR). Relative changes in blood flow were determined from measurements of vessel diameter and red blood cell velocity. Venular hemoglobin oxygen saturation measurements were performed by using in vivo spectrophotometric techniques. The relative dilation [times control (xCT)] of arteriolar vessels during contractions was as large or greater in SHR than in normotensive rats (Wistar-Kyoto), as were the increases in blood flow (2 Hz, 3.50 +/- 0.69 vs. 3.00 +/- 1.05 xCT; 4 Hz, 10.20 +/- 3.06 vs. 9.00 +/- 1.48 xCT; 8 Hz, 16.40 +/- 3.95 vs. 10.70 +/- 2.48 xCT). Venular hemoglobin oxygen saturation was lower in the resting muscle of SHR than of Wistar-Kyoto rats (31.0 +/= 3.0 vs. 43.0 +/- 1.9%) but was higher in SHR after 4- and 8-Hz contractions (4 Hz, 52.0 +/- 4.8 vs. 43.0 +/- 3.6%; 8 Hz, 51.0 +/- 4.6 vs. 41.0 +/- 3.6%). Therefore, an excess in oxygen delivery occurs relative to oxygen use during muscle contractions in SHR. The previous and current results can be reconciled by considering the possibility that oxygen exchange is limited in SHR by a decrease in anatomic or perfused capillary density, arteriovenular shunting of blood, or decreased transit time of red blood cells through exchange vessels.


Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 676
Author(s):  
Kunanya Masodsai ◽  
Yi-Yuan Lin ◽  
Sih-Yin Lin ◽  
Chia-Ting Su ◽  
Shin-Da Lee ◽  
...  

This study aimed to investigate the aging-related endothelial dysfunction mediated by insulin and insulin-like growth factor-1 (IGF-1) and antioxidant deficiency in hypertension. Male spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar–Kyoto rats (WKYs) were randomly divided into 24-week-old (younger) and 48-week-old (older) groups, respectively. The endothelial function was evaluated by the insulin- and IGF-1-mediated vasorelaxation of aortic rings via the organ bath system. Serum levels of nitric oxide (NO), malondialdehyde (MDA), catalase, and total antioxidant capacity (TAC) were examined. The insulin- and IGF-1-mediated vasorelaxation was significantly impaired in both 24- and 48-week-old SHRs compared with age-matched WKYs and was significantly worse in the 48-week-old SHR than the 24-week-old SHR. After pretreatments of phosphoinositide 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the insulin- and IGF-1-mediated vasorelaxation became similar among four groups. The serum level of MDA was significantly increased, while the NO, catalase, and TAC were significantly reduced in the 48-week-old SHR compared with the 24-week-old SHR. This study demonstrated that the process of aging additively affected insulin- and IGF-1-mediated endothelial dysfunction in SHRs, which could be partly attributed to the reduced NO production and antioxidant deficiency.


1991 ◽  
Vol 81 (1) ◽  
pp. 107-112 ◽  
Author(s):  
K. Fujito ◽  
M. Yokomatsu ◽  
N. Ishiguro ◽  
H. Numahata ◽  
Y. Tomino ◽  
...  

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.


2009 ◽  
Vol 110 (1) ◽  
pp. 224-234 ◽  
Author(s):  
Mehdi S. Hazari ◽  
Najwa Haykal-Coates ◽  
Darrell W. Winsett ◽  
Daniel L. Costa ◽  
Aimen K. Farraj

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