Estrogen enhances baroreflex control of heart rate in conscious ovariectomized rats

1998 ◽  
Vol 76 (4) ◽  
pp. 381-386 ◽  
Author(s):  
Mahmoud M El-Mas ◽  
Abdel A Abdel-Rahman

In previous studies, we have shown that the baroreflex control of heart rate is significantly attenuated in females compared with age-matched males. This study investigated the role of estrogen in the modulation of baroreflex function in conscious unrestrained rats. Baroreflex-mediated decreases in heart rate in response to increments in blood pressure evoked by phenylephrine were evaluated in conscious freely moving male and female Sprague-Dawley rats as well as in ovariectomized rats. The effect of a 2-day 17 beta -estradiol (50 µg ·kg-1 ·day-1, s.c.) or vehicle treatment on baroreflex sensitivity was investigated in ovariectomized rats. Intravenous bolus doses of phenylephrine (1-16 µg/kg) elicited dose-dependent pressor and bradycardic responses in all groups of rats. Regression analysis of the baroreflex curves relating increments in blood pressure to the associated heart rate responses revealed a significantly (p < 0.05) smaller baroreflex sensitivity in female compared with male rats (-1.22 ± 0.07 and -1.85 ± 0.15 beats ·min-1 ·mmHg-1, respectively), suggesting an attenuated baroreflex function in females. In age-matched ovariectomized rats, baroreflex sensitivity showed further reduction (-0.93 ± 0.02 beats ·min-1 ·mmHg-1). Treatment of ovariectomized rats with 17 beta -estradiol significantly (p < 0.05) enhanced the baroreflex sensitivity (-1.41 ± 0.16 beats ·min-1 ·mmHg-1) to a level that was slightly higher than that of sham-operated female rats. Furthermore, baroreflex sensitivity of ovariectomized estradiol-treated rats was not significantly different from that of age-matched male rats. The vehicle, on the other hand, had no effect on baroreflex sensitivity of ovariectomized rats. These data support our earlier findings that sexual dimorphism exists in baroreflex control of heart rate. More importantly, the present study provides experimental evidence that suggests a facilitatory role for estrogen in the modulation of baroreflex function.Key words: rat, gender, baroreflex sensitivity, 17 beta -estradiol, ovariectomy.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 727-727
Author(s):  
Ovidiu Baltatu ◽  
Ben J Janssen ◽  
Ralph Plehm ◽  
Detlev Ganten ◽  
Michael Bader

P191 The brain renin-angiotensin system (RAS) system may play a functional role in the long-term and short-term control of blood pressure (BPV) and heart rate variability (HRV). To study this we recorded in transgenic rats TGR(ASrAOGEN) with low brain angiotensinogen levels the 24-h variation of BP and HR during basal and hypertensive conditions, induced by a low-dose s.c. infusion of angiotensin II (Ang II, 100 ng/kg/min) for 7 days. Cardiovascular parameters were monitored by telemetry. Short-term BPV and HRV were evaluated by spectral analysis and as a measure of baroreflex sensitivity the transfer gain between the pressure and heart rate variations was calculated. During the Ang II infusion, in SD but not TGR(ASrAOGEN) rats, the 24-h rhythm of BP was inverted (5.8 ± 2 vs. -0.4 ± 1.8 mm Hg/group of day-night differences of BP, p< 0.05, respectively). In contrast, in both the SD and TGR(ASrAOGEN) rats, the 24-h HR rhythms remained unaltered and paralleled those of locomotor activity. The increase of systolic BP was significantly reduced in TGR(ASrAOGEN) in comparison to SD rats as previously described, while the HR was not altered in TGR(ASrAOGEN) nor in SD rats. The spectral index of baroreflex sensitivity (FFT gain between 0.3-0.6 Hz) was significantly higher in TGR(ASrAOGEN) than SD rats during control (0.71 ± 0.1 vs. 0.35 ± 0.06, p<0.05), but not during Ang II infusion (0.6 ± 0.07 vs. 0.4 ± 0.1, p>0.05). These results demonstrate that the brain RAS plays an important role in mediating the effects of Ang II on the circadian variation of BP. Furthermore these data are consistent with the view that the brain RAS modulates baroreflex control of HR in rats, with AII having an inhibitory role.


Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Fatima Ryalat ◽  
N Cruz-Diaz ◽  
W Graham ◽  
T Gwathmey-Williams ◽  
P E Gallagher ◽  
...  

Aldosterone plays a significant role in hypertension and target organ damage. Aldosterone antagonists are used in the management of heart failure. However, neither the influence of age nor sex on aldosterone pathophysiology is well understood. We investigated the changes in circulating aldosterone with age and its association with cardiovascular function, using male and female hypertensive renin transgenic (mRen2)27 rats and SD rats at 20 and 50 weeks of age. Both male (22 ± 3 vs. 12 ± 2 ng/dL, n = 9 - 12, p < 0.05) and female (59 ± 10 vs. 23 ± 8 ng/dL, n = 6 - 10, p < 0.05) hypertensive rats had higher serum aldosterone compared with SD rats at 20 weeks of age. At 50 weeks of age, the difference persisted in the hypertensive female rats (63 ± 8 vs. SD: 33 ± 7 ng/dL, n = 6 - 7, p < 0.05), but not in the males. SD male rats have higher systolic blood pressure (SBP) as they age, and consequently develop cardiac diastolic dysfunction associated with higher aldosterone at 50 weeks compared to 20 weeks (28 ± 3 vs. 12 ± 2 ng/dL, n = 7 - 9, p < 0.05). This aging effect on aldosterone was not significant in the other groups. We showed previously that SD males treated with polyphenol rich muscadine grape extract (MGE) have lower aldosterone, less aortic stiffness and better cardiac diastolic function (E/e’) than controls at the older age; the MGE effect was not seen in (mRen2)27 males. Sex differences in aldosterone were not significant in the SD rats at either time point. However, (mRen2)27 female rats had higher aldosterone than (mRen2)27 males at both 20 weeks (59 ± 10 vs. 22 ± 3 ng/dL, n = 10 - 12, p < 0.05) and 50 weeks (63 ± 8 vs. 31 ± 7 ng/dL, n = 6 - 7, p < 0.05), despite the lack of significant differences in SBP. (mRen2)27 female rats preserve cardiac function better than males throughout their life span, while males develop indices of heart failure. Our data suggest that lower aldosterone levels in hypertensive males compared with females do not protect against the higher lifetime burden of elevated SBP and also may reflect different mechanisms controlling circulating aldosterone between sexes. In addition, data suggest a potential therapeutic effect of MGE in the management of age-associated moderate hypertension.


2001 ◽  
Vol 280 (5) ◽  
pp. H2061-H2068 ◽  
Author(s):  
C. Michael Foley ◽  
Richard M. McAllister ◽  
Eileen M. Hasser

The effect of thyroid status on arterial baroreflex function and autonomic contributions to resting blood pressure and heart rate (HR) were evaluated in conscious rats. Rats were rendered hyperthyroid (Hyper) or hypothyroid (Hypo) with triiodothyronine and propylthiouracil treatments, respectively. Euthyroid (Eut), Hyper, and Hypo rats were chronically instrumented to measure mean arterial pressure (MAP), HR, and lumbar sympathetic nerve activity (LSNA). Baroreflex function was evaluated with the use of a logistic function that relates LSNA or HR to MAP during infusion of phenylephrine and sodium nitroprusside. Contributions of the autonomic nervous system to resting MAP and HR were assessed by blocking autonomic outflow with trimethaphan. In Hypo rats, the arterial baroreflex curve for both LSNA and HR was shifted downward. Hypo animals exhibited blunted sympathoexcitatory and tachycardic responses to decreases in MAP. Furthermore, the data suggest that in Hypo rats, the sympathetic influence on HR was predominant and the autonomic contribution to resting MAP was greater than in Eut rats. In Hyper rats, arterial baroreflex function generally was similar to that in Eut rats. The autonomic contribution to resting MAP was not different between Hyper and Eut rats, but predominant parasympathetic influence on HR was exhibited in Hyper rats. The results demonstrate baroreflex control of LSNA and HR is attenuated in Hypo but not Hyper rats. Thyroid status alters the balance of sympathetic to parasympathetic tone in the heart, and the Hypo state increases the autonomic contributions to resting blood pressure.


2014 ◽  
Vol 307 (11) ◽  
pp. H1539-H1546 ◽  
Author(s):  
Amy C. Arnold ◽  
Debra I. Diz

The decline in cardiovagal baroreflex function that occurs with aging is accompanied by an increase in circulating leptin levels. Our previous studies showed that exogenous leptin impairs the baroreflex sensitivity for control of heart rate in younger rats, but the contribution of this hormone to baroreflex dysfunction during aging is unknown. Thus we assessed the effect of bilateral leptin microinjection (500 fmol/60 nl) within the solitary tract nucleus (NTS) on the baroreflex sensitivity in older (66 ± 2 wk of age) urethane/chloralose anesthetized Sprague-Dawley rats with elevated circulating leptin levels. In contrast to the 63% reduction observed in younger rats, leptin did not alter the baroreflex sensitivity for bradycardia evoked by phenylephrine in older rats (0.76 ± 0.19 baseline vs. 0.71 ± 0.15 ms/mmHg after leptin; P = 0.806). We hypothesized that this loss of sensitivity reflected endogenous suppression of the baroreflex by elevated leptin, rather than cardiovascular resistance to the peptide. Indeed, NTS administration of a leptin receptor antagonist (75 pmol/120 nl) improved the baroreflex sensitivity for bradycardia in older rats (0.73 ± 0.13 baseline vs. 1.19 ± 0.26 at 10 min vs. 1.87 ± 0.32 at 60 min vs. 1.22 ± 0.54 ms/mmHg at 120 min; P = 0.002), with no effect in younger rats. There was no effect of the leptin antagonist on the baroreflex sensitivity for tachycardia, responses to cardiac vagal chemosensitive fiber activation, or resting hemodynamics in older rats. These findings suggest that the actions of endogenous leptin within the NTS, either produced locally or derived from the circulation, contribute to baroreflex suppression during aging.


Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 700-700
Author(s):  
Aurea S Couto ◽  
Ovidiu Baltatu ◽  
Robson A S Santos ◽  
Detlev Ganten ◽  
Michael Bader ◽  
...  

P42 The potential importance of permanent alteration of the brain renin-angiotensin system on angiotensin (Ang) II and Ang-(1-7) effects at the level of the nucleus tractus solitarii (NTS) was investigated in transgenic rats with a deficit in brain angiotensinogen production TGR(ASrAOGEN) (TGR). Ang II (10 pmol), Ang-(1-7) (10 pmol) or NaCl (0.9%/ 50 nl) were microinjected into the NTS of urethane-anesthetized TGR (n=28) and Sprague-Dawley (SD, n=22) rats. Mean arterial pressure (MAP) and heart rate (HR) were measured via a femoral artery catheter and the baroreflex control of heart rate was evaluated after increases in MAP induced by phenylephrine (baroreflex bradycardia). Ang II microinjections into the NTS of the TGR induced a higher decrease in MAP and HR (-37 ± 5 mmHg and -69 ± 12.5 beats/min, respectively) in comparison with SD rats (-18 ± 1 mmHg and -51 ± 11 beats/min, respectively). In contrast, changes after Ang-(1-7) microinjections into the NTS of TGR (-6 ± 1 mmHg and -13 ± 5 beats/min) were significantly smaller than that induced in SD (-11 ± 2 mmHg and -24 ± 8 beats/min.). The baroreflex sensitivity was accentuated in TGR in comparison to SD rats (0.69 ± 0.06 vs. 0.44 ± 0.03 ms/ mmHg). Ang II microinjection into the NTS produced similar attenuation in the baroreflex bradycardia in both SD (0.28 ± 0.07 vs. 0.5 ± 0.07 ms/ mmHg, before injection) and TGR (0.44 ± 0.1 vs. 0.82 ± 0.1ms/ mmHg, before injection). Ang-(1-7) microinjection elicited a facilitation of the baroreflex bradycardia in SD (0.62 ± 0.1 vs. 0.4 ± 0.03 ms/ mmHg, before injection). However in TGR, baroreflex bradycardia after Ang-(1-7) was not different from saline microinjection. These results indicate that a permanent inhibition of angiotensinogen synthesis in the brain can lead to a functional up-regulation of Ang II receptors. However, the putative Ang-(1-7) receptors seem to be desensitized in the NTS of these transgenic rats. The alterated baroreflex sensitivity, both before and after Ang microinjection, indicates the functionally relevant decrease in brain Ang in TGR and supports differential regulatory mechanisms for the effects of the two Ang peptides.


1991 ◽  
Vol 261 (5) ◽  
pp. R1118-R1125 ◽  
Author(s):  
K. Toba ◽  
J. T. Crofton ◽  
M. Inoue ◽  
L. Share

This study was performed to investigate further the mechanisms underlying the sexual dimorphism of the pressor responses to vasopressin. We have confirmed our earlier findings that the pressor response to graded infusions of vasopressin in conscious unrestrained male rats is similar to that in estrous females and greater than in diestrus, proestrus, and metestrus. This difference was due primarily to greater increases in total peripheral resistance (TPR) in males and estrous females, since there were no sex- or cycle-related differences in the vasopressin-induced reductions in cardiac output. Gonadectomy was without effect in males but, in females, increased blood pressure responses to vasopressin to levels found in males. Chronic treatment of ovariectomized rats with estradiol reduced pressor responsiveness to vasopressin; treatment with progesterone was without effect. These differences were also due to differences in TPR. It is concluded that the sex- and cycle-dependent differences in vasopressin-induced increases in blood pressure are due largely to attenuation of increases in TPR by estrogen.


1995 ◽  
Vol 268 (4) ◽  
pp. H1606-H1612 ◽  
Author(s):  
G. Parati ◽  
A. Frattola ◽  
M. Di Rienzo ◽  
P. Castiglioni ◽  
A. Pedotti ◽  
...  

The effects of aging on the dynamic modulation of baroreflex sensitivity over 24 h was assessed in eight elderly (mean age +/- SD, 63.9 +/- 3.2 yr) and in eight young (23.9 +/- 6.1 yr) mild or moderate essential hypertensive patients, who were subject to a 24-h intra-arterial (Oxford technique) blood pressure recording in ambulatory conditions. The sensitivity of baroreflex control of the heart rate was dynamically assessed by quantifying 1) the slope of the regression line between pulse interval (the reciprocal of heart rate) and systolic blood pressure changes over spontaneously occurring hypertension-bradycardia or hypotension-tachycardia sequences (time domain analysis) and 2) the ratio between spectral-powers of pulse interval and systolic blood pressure around 0.1 Hz (alpha-coefficient: frequency domain analysis). The 24-h average sequence slope was lower in old than in young individuals (4.4 +/- 0.5 vs. 9.9 +/- 1.3 and 4.8 +/- 0.7 vs. 8.4 +/- 1.4 ms/mmHg for hypertension-bradycardia and hypotension-tachycardia sequences, respectively; P < 0.05 for both). Similar results were obtained by using the alpha-coefficient approach. The marked nighttime increase in baroreflex sensitivity observed in young individuals was much less evident in the elderly. Thus 24-h baroreflex sensitivity is markedly impaired by aging. The impairment becomes manifest also as an inability to increase baroreflex sensitivity at night.


2019 ◽  
Vol 3 (s1) ◽  
pp. 21-21
Author(s):  
Jonathas Fernandes Queiroz Almeida ◽  
Aline Souza ◽  
Hong Ji ◽  
Kathryn Sandberg

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to determine if there are any sex differences in the pathophysiological effects of sFR. METHODS/STUDY POPULATION: Male Fischer rats (4-month-old) were maintained on a control (CT) (ad libitum regular chow; n=8) or sFR (60% reduction of daily food intake, n=8) diet for 2 weeks. On days 1, 2, 3 and 14, the rats were placed in metabolic cages for food and water intake and 24-hour urine collection. Body weight (BW) is measured daily. After 2 weeks, the animals are given free access to normal chow for 3 months. Short-term and long-term effects of sFR on blood pressure and heart rate will be measured. RESULTS/ANTICIPATED RESULTS: After 2 weeks, the male CT group gained 7% BW (p <0.05), while BW in the sFR males was reduced by 12% (p<0.05 vs. CT). In contrast, female controls did not gain BW while the sFR females lost 18% of their BW. Water intake was reduced by 35%, which was similar to the reduction in females (p=0.18). The hematocrit of sFR male rats was higher (51.1%) than the CT group (45.2%, p<0.05), which was most likely due to the 6% reduction in plasma volume. A similar effect on hematocrit was observed in sRF females. Similarly, also to female rats, sFR had no effect on Na+ and K+ plasma or urine concentrations by day 14 in the male rats. DISCUSSION/SIGNIFICANCE OF IMPACT: sFR has similar effects on electrolyte balance in males and females. Ongoing studies will determine if there is any sex difference in the effects of sFR on blood pressure, heart rate and susceptibility to hypertension and cardiac injury.


1999 ◽  
Vol 77 (5) ◽  
pp. 358-366 ◽  
Author(s):  
Abdel A Abdel-Rahman

In a previous clinical study we have demonstrated a significantly lower baroreflex-mediated bradycardic response in young women compared with men. The present study determined whether sexual dimorphism in baroreflex sensitivity in young rats also covers the reflex tachycardic response. The study was then extended to test the hypothesis that an attenuated cardiac cholinergic component of the baroreflex heart rate response in females may account for the gender difference. Baroreflex sensitivity (BRS) was expressed as the regression coefficient of the reciprocal relationship between evoked changes in blood pressure and heart rate. BRS measured in conscious rats with phenylephrine (BRSPE) and nitroprusside (BRSNP) represented the reflex bradycardic and tachycardic responses, respectively. Female rats exhibited significantly lower BRSPE compared with male rats (-1.53 ± 0.1 vs. -2.36 ± 0.13 beats·min-1·mmHg-1; p < 0.05) but similar BRSNP (-2.60 ± 0.20 vs. -2.29 ± 0.17 beats·min-1·mmHg-1). Blockade of cardiac muscarinic receptors with atropine methyl bromide elicited greater attenuation of BRSPE in male than in female rats (72 ± 4.6 vs. 53 ± 6.7% inhibition; p < 0.01) and abolished the gender difference. In male rats cardiac muscarinic blockade attenuated BRSPE significantly more than did cardiac beta-adrenergic receptor blockade with propranolol (72 ± 4.6 vs. 43 ± 2.7; p < 0.01), which suggests greater dependence of BRSPE on the parasympathetic component. In females, muscarinic and beta-adrenergic blockade elicited similar attenuation of BRSPE. The findings suggest that (i) BRS is differentially influenced by gender; female rats exhibit substantially lower BRSPE but similar BRSNP compared with age-matched male rats and (ii) the sexual dimorphism in BRSPE results, at least partly, from a smaller increase in vagal outflow to the heart in response to baroreceptor activation.Key words: gender difference, baroreflex sensitivity, vagal outflow, conscious rats.


1982 ◽  
Vol 60 (2) ◽  
pp. 208-212 ◽  
Author(s):  
Alexis Gairard ◽  
Alain Berthelot ◽  
René Schleiffer ◽  
Fanny Pernot

In male Sprague–Dawley rats, hypertensive development was diminished for 10 weeks when parathyroidectomy (PTX) was performed 1 week before deoxycorticosterone plus saline (DOCA + NaCl) treatment. In young spontaneously hypertensive male rats (SHR, Okamoto strain) parathyroidectomy performed after weaning lessened hypertensive levels and lowered heart rate for 24 weeks. When mineralocorticoid or genetic hypertension was established, parathyroidectomy did not significantly change blood pressure levels. High dietary calcium in PTX–SHR rats reestablished normal serum calcium but not systolic blood pressure to the level of sham SHR. From our present and previously reported results, it appears that the parathyroid gland is necessary for the total development of hypertension in both models.


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