Hyperhomocysteinaemia‐induced Cardiovascular Changes in Rats

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.

Homocysteine Thiolactone Induces Cardiac Dysfunction: Role of Oxidative Stress

“…[26][27][28] In addition, our results demonstrated that HcyT treatment did not change heart weight and LV mass, but there was an important reduction in the FS.…”

The Cardiovascular Effect of Systemic Homocysteine Is Associated with Oxidative Stress in the Rostral Ventrolateral Medulla

“…HCY, a sulfur amino acid which is synthesized from dietary methionine by a process of demethylation [ 30 ], has been demonstrated to be closely involved in the abnormal cardiovascular autonomic control and increased arterial pressure [ 31 ]. Increase in resting BP caused by hyperhomocysteinemia was totally reversed by interference with β 1-adrenoceptor antagonist atenolol, indicating that the HCY-relative hypertension is associated with the increase in sympathetic activity [ 32 ]. It has been well established that ROS has a pivotal role in the activation of the central and peripheral sympathetic nerve system [ 12 , 33 ].…”

Short-term nutritional folate deficiency in rats has a greater effect on choline and acetylcholine metabolism in the peripheral nervous system than in the brain, and this effect escalates with age

“…Our present data demonstrate that folate deficiency potentiates age-related increases in acetylcholine levels in the hearts of adult rats. Studies in rats [9, 10, 31, 32, 52, 53] and humans [54–57] show that folate deficiency results in hyperhomocysteinemia, which, in turn, is associated with the risk of hypertension.…”