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Published on: December 5, 2017
Hyperhomocysteinaemia-induced cardiovascular changes in rats
Leonardo B M Resstel1, Claudia R de Andrade, Renato Haddad
1Department of Pharmacology, School of Medicine, University of São Paulo, Ribeiraão Preto, Brazil.
Insights
Elevated homocysteine (HHcys) in rats increased blood pressure, heart rate, and baroreflex activity. These cardiovascular changes were reversible, indicating moderate HHcys impacts cardiovascular function.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Pharmacology
Background:
- Elevated plasma homocysteine is linked to increased cardiovascular risks.
- Hyperhomocysteinaemia (HHcys) may affect cardiovascular system activity.
- Understanding HHcys effects on cardiovascular function is crucial for risk assessment.
Purpose of the Study:
- To investigate the impact of moderate HHcys on cardiovascular system activity in rats.
- To determine the effects of HHcys on arterial blood pressure, heart rate, baroreflex, and vascular reactivity.
- To explore the role of cardiac sympathetic activity in HHcys-induced hypertension.
Main Methods:
- Male Wistar rats were treated with dl-homocysteine thiolactone (DL-HT) to induce moderate HHcys.
- Cardiovascular parameters including arterial blood pressure, heart rate, and baroreflex gain were measured.
- Vascular reactivity was assessed using pressor and depressor agents, with and without DL-HT washout.
Main Results:
- Moderate HHcys significantly increased baseline arterial blood pressure, heart rate, and baroreflex gain.
- Vascular responsiveness to phenylephrine, sodium nitroprusside, and acetylcholine was altered in HHcys rats.
- HHcys-related hypertension was reversed by atenolol, suggesting increased cardiac sympathetic activity.
Conclusions:
- Moderate HHcys induces significant cardiovascular changes, including hypertension and altered baroreflex activity.
- HHcys affects vascular responsiveness and is associated with increased cardiac sympathetic activity.
- The observed cardiovascular alterations are reversible upon cessation of DL-HT treatment.
Abstract:
(1) Increased plasma homocysteine content and increased blood pressure are independently associated with higher cardiovascular risks. The present study was designed to determine the effects of hyperhomocysteinaemia (HHcys) on the activity of the cardiovascular system in rats. (2) Using male Wistar rats, the effect of moderate HHcys, induced by treating rats with dl-homocysteine thiolactone (DL-HT; 1 g/kg per day) for 15 days, on arterial blood pressure, heart rate, baroreflex and vascular reactivity was determined. (3) Hyperhomocysteinaemia was observed after 15 days of treatment. Baseline arterial blood pressure and heart rate values of HHcys animals were significantly increased after 15 days of treatment. Plasma homocysteine and cardiovascular parameters returned to control values after termination of treatment. Baroreflex gain was significantly enhanced in HHcys rats. The pressor effect of an i.v. infusion of phenylephrine (50 mg/kg per mL) was decreased in HHcys rats and returned to control values after washout of DL-HT. Hypotensive responses to i.v. infusions of sodium nitroprusside (70 mg/kg per mL) or acetylcholine (10 mg/kg per mL) were increased in HHcys animals and returned to control values after washout of DL-HT. The increase in resting arterial blood pressure associated with the moderate HHcys was reversed by treatment with the b1-adrenoceptor antagonist atenolol, suggesting that HHcys-related hypertension is related to increase in cardiac sympathetic activity. (4) The present study showed significantly increased arterial blood pressure, heart rate and baroreflex activity in the early phase of moderate HHcys. In addition, HHcys was associated with alterations of vascular responsiveness to pressor and depressor agents, as well as increased cardiac sympathetic activity. The fact that cardiovascular changes observed in HHcys were reversed after DL-HT washout indicate that moderate HHcys evokes cardiovascular changes.
