[Show abstract][Hide abstract] ABSTRACT: Studies have revealed that apelin is a novel multifunctional peptide implicated both in blood pressure (BP) regulation and cardiac function control. Evidence shows that apelin and its receptor (APJ) in the rostral ventrolateral medulla (RVLM) may play an important role in central BP regulation; however, its role is controversial and very few reports have shown the relationship between acupuncture and apelin. Our study aims to both investigate the apelinergic system role in stress-induced hypertension (SIH) and determine whether acupuncture therapy effects on hypertension involve the apelinergic system in the RVLM. We established the stress-induced hypertensive rat (SIHR) model using electric foot-shock stressors with noise interventions. The expression of both apelin and the APJ receptor in the RVLM neurons was examined by immunohistochemical staining and Western blots. The results showed apelin expression increased remarkably in SIHR while APJ receptor expression showed no significant difference between control and SIHR groups. Microinjection of apelin-13 into the RVLM of control rats or SIHR produced pressor and tachycardic effects. Furthermore, effects induced by apelin-13 in SIHR were significantly greater than those of control rats. In addition, repetitive electroacupuncture (EA) stimulation at the Zusanli (ST-36) acupoint attenuated hypertension and apelin expression in the RVLM in SIHR; it also attenuated the pressor effect elicited by exogenous apelin-13 microinjection in SIHR. The results suggest that augmented apelin in the RVLM was part of the manifestations of SIH; the antihypertensive effects of EA might be associated with the attenuation of apelin expression and function in the RVLM, which might be a novel role for EA in SIH setting.
Full-text · Article · Jun 2013 · Brain research bulletin
[Show abstract][Hide abstract] ABSTRACT: 1. Nitric oxide (NO), a gas transmitter, modulates many physiological processes, including the central regulation of cardiovascular activity. However, the mechanisms underlying the regulation of cardiovascular activity remain relatively unexplored. In the present study, we hypothesized that central NO-dependent sympathetic inhibition is mediated by activation of adenosine A2A receptors (A2AR) and inhibition of acetylcholine (ACh) release in the rostral ventrolateral medulla (RVLM).
2. l-Arginine (l-Arg; an NO donor; 100 nmol/100 nL) was microinjected into the RVLM of male Sprague–Dawley rats and heart rate variability (HRV) was assessed as an index of cardiac sympathovagal balance. Following microinjection of l-Arg, decreases were seen in mean arterial pressure (MAP), heart rate (HR) and the ratio of the low- to high-frequency components (LF/HF) of HRV. Pretreatment of rats with SCH58261 (40 pmol/60 nL into the RVLM), a competitive antagonist of the A2AR, attenuated these effects.
3. Western blot analysis and ELISA revealed that adenosine and A2AR levels increased in the RVLM following l-Arg microinjection, whereas ACh and muscarinic M1 receptor levels decreased significantly, in parallel with the cardiovascular responses to l-Arg microinjection. The decrease in ACh levels was abolished by SCH58261 pretreatment.
4. Microinjection of NG-nitro-l-arginine methyl ester (a non-selective inhibitor of NO synthase; 15 nmol/100 nL) into the RVLM significantly increased MAP, HR and sympathetic activity, as evidenced by HRV (LF, HF and the LF/HF ratio were all increased).
5. The results indicate that the central NO/NO synthase system in the RVLM may modulate cardiovascular activity by activating the A2AR, which subsequently inhibits activation of the muscarinic M1 receptor.
Full-text · Article · Mar 2011 · Clinical and Experimental Pharmacology and Physiology