Effect of Ovariectomy on Blood Pressure and Venous Tone in Female Spontaneously Hypertensive Rats

Martin, Douglas; Redetzke, Rebecca A.; Vogel, Erin; Mark, Connie J.; Eyster, Kathleen M.

doi:10.1038/ajh.2008.237

Cited by 8 publications

(10 citation statements)

References 37 publications

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“…However, we observed that ovariectomy did not further affect blood pressure levels in female hypertensive rats. Our findings are consistent with those of some studies that showed that hypertension was not exacerbated in hypertensive rats after ovariectomy [32,33]. Indeed, menopause is characterized by increases in blood pressure [1].…”

Section: Discussionsupporting

confidence: 93%

The Coexistence of Hypertension and Ovariectomy Additively Increases Cardiac Apoptosis

Lin

Cheng

et al. 2016

IJMS

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To investigate whether the coexistence of hypertension and ovariectomy will increase cardiac Fas receptor and mitochondrial-dependent apoptotic pathways, histopathological analysis, the TUNEL assay and Western blotting were performed on the excised hearts from three groups of female spontaneously hypertensive rats (SHR), which were divided into a sham-operated group (SHR-Sham), bilaterally ovariectomized group (SHR-OVX) and normotensive Wistar Kyoto rats (WKY). Compared with the WKY group, the SHR-Sham group exhibited decreased protein levels of ERα, ERβ, p-Akt/Akt, Bcl-2, Bcl-xL and p-Bad and decreased further in the SHR-OVX group, as well as protein levels of t-Bid, Bak, Bad, Bax, cytochrome c, activated caspase-9 and activated caspase-3 (mitochondria-dependent apoptosis) increased in the SHR-Sham group and increased further in the SHR-OVX group. Compared with the WKY group, protein levels of Fas ligand, TNF-α, Fas death receptors, TNFR1, FADD and activated caspase-8 (Fas receptor-dependent apoptosis) increased in the SHR-Sham group, but did not increase in the SHR-OVX group, except Fas ligand and TNF-α. The coexistence of hypertension and ovariectomy attenuated the estrogen receptor survival pathway and appeared to additively increase the cardiac mitochondria-dependent, but not the Fas receptor-dependent apoptosis pathway, which might provide one possible mechanism for the development of cardiac abnormalities in hypertensive postmenopausal women.

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Section: Discussionsupporting

confidence: 93%

The Coexistence of Hypertension and Ovariectomy Additively Increases Cardiac Apoptosis

Lin

Cheng

et al. 2016

IJMS

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“…Indeed, hypertension is a major risk for diastolic dysfunction and left ventricular hypertrophy and it is a common correlate to heart failure with preserved ejection (Kane et al, ; Lalande & Johnson, ), particularly among aging women (Katholi & Couri, ; Redfield, Jacobsen, Borlaug, Rodeheffer, & Kass, ). Importantly, and consistent with others, BPs over the course of the study in both strains were not affected by OVX (Martin, Redetzke, Vogel, Mark, & Eyster, ; Reckelhoff, ). Consistent with our previous study, worsening of diastolic function, defined by reductions in e′ and increases E/e′, was observed in WKY rats while LV hypertrophy (Wang, da Silva, et al, ), expressed by increases in LV mass, was apparent in both rat strains after OVX.…”

Section: Discussionsupporting

confidence: 89%

Blunting of estrogen modulation of cardiac cellular chymase/RAS activity and function in SHR

Ahmad

Sun

Lin

et al. 2017

Journal Cellular Physiology

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The relatively low efficacy of ACE-inhibitors in the treatment of heart failure in women after estrogen loss may be due to their inability to reach the intracellular sites at which angiotensin (Ang) II is generated and/or the existence of cell-specific mechanisms in which ACE is not the essential processing pathway for Ang II formation. We compared the metabolic pathway for Ang II formation in freshly isolated myocytes (CMs) and non-myocytes (NCMs) in cardiac membranes extracted from hearts of gonadal-intact and ovariectomized (OVX) adult WKY and SHR rats. Plasma Ang II levels were higher in WKY vs. SHR (strain effect: WKY: 62 ± 6 pg/ml vs. SHR: 42 ± 9 pg/ml; p < 0.01), independent of OVX. The enzymatic activities of chymase, ACE, and ACE2 were higher in NCMs versus CMs, irrespective of whether assays were performed in cardiac membranes from WKY or SHR or in the presence or absence of OVX. E2 depletion increased chymase activity, but not ACE activity, in both CMs and NCMs. Moreover, cardiac myocyte chymase activity associated with diastolic function in WKYs and cardiac structure in SHRs while no relevant functional and structural relationships between the classic enzymatic pathway of Ang II formation by ACE or the counter-regulatory Ang-(1-7) forming path from Ang II via ACE2 were apparent. The significance of these novel findings is that targeted cell-specific chymase rather than ACE inhibition may have a greater benefit in the management of HF in women after menopause.

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“…Since all anesthetics, including isoflurane(37), may influence vascular reactivity, we decided to measure blood pressure under the same conditions as the vascular responses, namely under the influence of isoflurane. However, it is equally important to note that the pattern of blood pressure in the sham operated and gonadectomized SHR is similar to that which we (7, 8, 11, 12, 38) and others (e.g.,(36, 39, 40)) have reported previously. Thus, we are reasonably confident that the blood pressures reported in this study accurately reflect the blood pressure responses to gonadectomy.…”

Section: Discussionsupporting

confidence: 86%

“…For example, some studies reported that estrogen attenuated hypertension development in the spontaneously hypertensive rat (SHR) (5, 6). In contrast other data, including our own, showed that ovariectomy did not raise blood pressure in female SHR (3, 4, 7, 8) when blood pressure was measured relatively soon (3-8 weeks) after ovariectomy. On the other hand, natural estrogen loss induces a slow increase in arterial blood pressure that is only fully expressed in older rats (9).…”

Section: Introductioncontrasting

confidence: 86%

Blood Pressure and Mesenteric Vascular Reactivity in Spontaneously Hypertensive Rats 7 Months After Gonadectomy

Tatchum-Talom

Eyster²,

Kost³

et al. 2011

Journal of Cardiovascular Pharmacology

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Objective-Sexual dimorphism in the degree of high blood pressure has been observed in both animal and human hypertension. However, the mechanisms are still poorly understood. We tested the hypothesis that long term loss of sex steroids promotes changes in mesenteric vascular reactivity that impact the maintenance of hypertension in the SHR. Methods-Male spontaneously hypertensive rats (SHR) were sham-operated (M-SHAM) or castrated (M-CX), and female SHR were sham-operated (F-SHAM) or ovariectomized (F-OVX) at 3 weeks of age. Seven months later, blood pressure (BP) was measured in anesthetized rats and vascular responsiveness was evaluated in the isolated perfused mesentery. Results-Mean arterial BP (mmHg) was significantly greater in M-SHAM (186±6) compared to F-SHAM (159±5). Gonadectomy reduced BP in male SHR (M-CX, 160±4), but had no significant effect in female SHR (F-OVX, 153±7). Norepinephrine induced constriction was similar in all groups. Gonadectomy attenuated serotonin-induced vasoconstriction in the mesentery. Acetylcholine (ACh)-and isoproterenol (ISO)-induced vasodilation was greater in female than male SHR. Ovariectomy of female SHR blunted ACh and ISO dilatory responses. ISO dose response curves were shifted to the left in castrated male SHR.Conclusions-Gonadectomy exerts long term effects on mesenteric vascular reactivity and hypertension in the SHR.

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Effect of Ovariectomy on Blood Pressure and Venous Tone in Female Spontaneously Hypertensive Rats

Abstract: Endogenous ovarian hormones effect a small reduction in MCFP. This effect does not appear to be mediated by adrenergic mechanisms.

Cited by 8 publications

References 37 publications

The Coexistence of Hypertension and Ovariectomy Additively Increases Cardiac Apoptosis

The Coexistence of Hypertension and Ovariectomy Additively Increases Cardiac Apoptosis

Blunting of estrogen modulation of cardiac cellular chymase/RAS activity and function in SHR

Blood Pressure and Mesenteric Vascular Reactivity in Spontaneously Hypertensive Rats 7 Months After Gonadectomy

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