Stress-induced reduction in ACE2 activity and raised hypothalamic activation in aging female rats: novel insights into the origins of hypertension following menopause
Notice bibliographique
Résumé
Introduction: The onset of menopause increases the development of cardiovascular diseases and hypertension. However, only a subpopulation of menopausal women develops these disorders. The origins of such distinct aging trajectories are unknown. Since stress has persistent and sex-specific effects on health, we hypothesized that early-life stress exacerbates the cardiovascular consequences of the loss of ovarian function in aging rats. Methodology: Neonatal maternal separation (NMS) is a clinically relevant model of early-life stress. Following birth, rats were either raised under standard conditions (CTRL) or subjected to NMS (3h/day from postnatal days 3 to 12). When the females reached 60 weeks (old age), we measured arterial blood pressure by the “tail-cuff” method. We then measured the activity of the angiotensin-converting enzyme (ACE) and its homolog ACE 2 in serum, two key enzymes involved in the homeostasis of the renin-angiotensin system (RAS). Finally, we compared the expression of FosB, a transcription factor indicating neuronal activity, in the paraventricular nucleus of the hypothalamus (PVN); this structure is involved in the development and maintenance of hypertension and regulation of stress responses. The PVN contains two major anatomical structures: magnocellular (vasopressin secretion) and parvocellular (neuroendocrine-related functional and central autonomic control). Results: The mean arterial blood pressure (MAP) of NMS females was 12% higher than CTRL but the heart rate was 9% lower. Interestingly, in our previous studies, this stress effect was not observed in young adults (8 weeks old). The catalyzed activity of ACE was similar between groups, but ACE2 activity was 60% lower in NMS. The number of neurons expressing FosB was 55% higher in the magnocellular region of the PVN in NMS females. Finally, we observed a strong negative correlation between ACE2 activity and MAP (r 2 = -0.71, p=0.002). Conclusions: Unlike CTRL, aged NMS females showed an increased risk of hypertension. The lower activity of ACE2 may lead to an accumulation of Angiotensin II, which stimulates the release of vasopressin. Vasopressin, in turn, inhibits the secretion of renin. Increased renin predisposes individuals to develop hypertension. The increased magnocellular activation of PVN indicated that the vasopressin and the RAS may be interacting and contributing increased MAP. Therefore, we conclude that loss of ovarian function reveals the effects of early-life stress on cardiovascular homeostasis in females. DAM is supported by the FRQ-S (268346) and the “Programme de complément de bourse” from RSRQ (2021-22). This research is supported by the Canadian Institutes of Health Research (RK). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».