ABSTRACT
AIM:To observe the effect of central prostaglandin E2(PGE2) on sympathetic activation in chronic heart failure (CHF) and to explore the underlying mechanism. METHODS:Male SD rats were subjected to coronary ar-tery ligation to induce heart failure (HF), and the intracerebroventricular infusion was performed by osmotic pump continu-ously. The rats in sham group and HF group were given artificial cerebrospinal fluid (0. 25 μL/h). The rats in HF plus treatment group was given celecoxib (CLB; 20 mg/h). After 4 weeks, the levels of PGE2 in cerebrospinal fluid ( CSF), the sympathetic nerve excitability and cardiac function were measured, and the changes of corticotropin-hormone releasing hormone ( CRH)-containing neurons activation and neurotransmitter contents in the hypothalamic paraventricular nucleus ( PVN) were also determined. RESULTS:Compared with the sham-operated rats, the HF rats had raised level of PGE2 in CSF, up-regulated renal sympathetic nerve activity and plasma norepinephrine, increased left ventricular end diastolic pres-sure, lung-to-body weight and right ventricular-to-body weight ratios, and decreased maximal increase and decreased rate of left ventricular pressure (P<0.05). In addition, the number of CRH positive neurons in PVN and the level of plasma ad-renocorticotropic hormone were higher in HF rats than those in sham-operated rats (P<0.05). After administration of CLB into the lateral ventricle of HF rats, the contents of PGE2 in CSF were significantly reduced, the number of activation CRH neurons in PVN was decreased, the excitability of sympathetic nerves was down-regulated and cardiac function was im-proved (P<0.05). Compared with the sham-operated rats, the content of glutamic acid in PVN of HF rats was increased, the content of γ-aminobutyric acid and the number of glutamate decarboxylase 67-positive neurons were decreased ( P<0.05). After the CLB was given, the above indexes were reversed (P<0.05). CONCLUSION:These findings indicate that in CHF, the increased central PGE2 may activate CRH-containing PVN neurons and contribute to the augmented sym-pathetic drive possibly by modulating the neurotransmitters within the PVN.
ABSTRACT
AIM: To observe the expression of corticotropin releasing hormone (CRH) within the paraventricular nucleus of hypothalamus (PVN) and to explore the relationship between the activated CRH-containing neurons and sympathetic activity in rats with heart failure (HF).METHODS: Healthy male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to induce HF, and chronic intracerebroventricular (ICV) infusion was performed by osmotic pump for 4 weeks.The rats in sham group and HF group were given vehicle (VEH;artificial cerebrospinal fluid 0.25 μL/h).The rats in HF plus treatment group were treated with CRH competitive inhibitor αh-CRH (15 mg/h).Meanwhile, the Lewis rats and Fischer 344 rats for control study also underwent coronary ligation to induce HF or sham surgery.After 4 weeks, left ventricular end-diastolic pressure (LVEDP) and maximum positive/negative change in pressure over time (±dp/dtmax) were determined.The right ventricular-to-body weight (RV/BW) and lung-to-body weight (lung/BW) ratios were calculated.The renal sympathetic nerve activity (RSNA) was recorded and the plasma norepinephrine (NE) level was measured.The expression of CRH in the PVN combined with the plasma adrenocorticotrophic hormone (ACTH) levels were measured.RESULTS: Compared with the sham-SD rats, the HF-SD rats had a greater number of CRH positive neurons in the PVN (accordingly the plasma ACTH levels were increased), accompanied by decreased ±dp/dtmax and increased RSNA, plasma NE, LVEDP, lung/BW and RV/BW.However, ICV treatment with αh-CRH attenuated these changes in the HF-SD rats (P<0.05).Compared with the sham-Fisher 344 rats, the HF-Fisher 344 rats also had a greater number of CRH positive neurons in the PVN (accordingly the plasma ACTH levels were increased).In addition, they had significantly increased RSNA and plasma NE level, higher LVEDP, RV/BW and lung/BW, and lower ±dp/dtmax (P<0.05).Compared with the SHAM-Lewis rats, the HF-Lewis rats had not significantly changed in the above parameters.CONCLUSION: In CHF, the CRH-containing neurons in PVN are activated, thus aggravating cardiac function by increasing sympathoexcitation.