Involvement of GABAergic and Adrenergic Neurotransmissions on Paraventricular Nucleus of Hypothalamus in the Control of Cardiac Function

Abstract

Sympathetic premotor neurons of the paraventricular hypothalamus (PVN) play a role in hemodynamics adjustments during changes in body fluid homeostasis. However, PVN contribution to the tonic control of cardiac function remains to be systematically studied. In this study, we assessed whether GABAergic and adrenergic synapses, known for being active in the PVN, are involved in the control of cardiac function. Adult male Wistar rats (250–350 g; n = 27) were anesthetized with urethane (1.2–1.4 g/kg i.p.) and underwent catheterization of femoral artery to record blood pressure and heart rate. The femoral vein was used to inject the vasoactive agents phenylephrine (10 μg/kg) and sodium nitroprusside (10 μg/kg) and to supplement anesthesia. The cardiac left ventricle was catheterized to record left ventricular pressure and its derivative. Craniotomy allowed for injections (100 nL) into the PVN of: muscimol (20 mM), bicuculline methiodide (0.4 mM), propranolol (10 mM), isoproterenol (100 μM), phentolamine (13 mM), phenylephrine (30 nM). We found that: (i) inhibition of PVN by muscimol, reduced arterial pressure, cardiac chronotropy and inotropy; (ii) disinhibition of PVN neurons by bicuculline evoked positive chronotropy and inotropy, and increase blood pressure; (iii) PVN alpha adrenergic receptors control cardiac chronotropy and inotropy; (iv) beta adrenergic receptors of the PVN do not influence cardiac function; (v) afterload does not contribute to the PVN-evoked inotropy. Our results indicate that the modulation of the activity of PVN neurons exerted by GABAergic and adrenergic mechanisms contribute to the control of cardiac function.

BDNF downregulates β-adrenergic receptor-mediated hypotensive mechanisms in the paraventricular nucleus of the hypothalamus

“…However, other studies found that microinjections of the ␤-adrenergic receptor agonist isoprenaline in WKY and SD rats had no effect on blood pressure (48, 82) but did increase baroreflex sensitivity in SD rats (82). On the other hand, PVN injections of the ␣ 1 -adrenergic receptor agonist phenylephrine or the nonselective ␣-adrenergic receptor antagonist phentolamine significantly increased renal sympathetic nerve activity and heart rate without an effect on blood pressure (10,48). Our experiments demonstrated that, in control GFP animals, selective catecholaminergic lesioning in the NTS induced a marked increase in blood pressure, whereas stimulation of ␤-adrenergic receptors in the PVN resulted in significant hypotensive responses.…”

Transcriptome Profile of Hippocampus in Rats Model of Acute Myocardial Ischemia in Response to Electroacupuncture

“…Increased activity at excitatory (eg, glutamatergic and cholinergic ) synapses has been linked to cardiovascular injury [48][49][50][51][52]. Similarly, serotonergic and GABAergic synapses in the CNS in uence cardiovascular activity [53][54][55]while central cholinergic transmission induces cardiovascular changes in hypertensive rats [56]. Our results demonstrate that the aberrant activity of hippocampal neurons induced by AMI can be at least partly mitigated by EA.Our data showed that the expression of multiple genes was altered by AMI and restored by EA treatment.…”

Contribution of DNA methylation in chronic stress‐induced cardiac remodeling and arrhythmias in mice

“…However, CRS not only triggered changes in the heart and peripheral nervous system; it also resulted in remodeling of central sites. The PVN is one of the most important brain centers that regulate sympathetic tone (45), stress response (46, 47), and cardiac function (48). The PVN and hypothalamus of CRS mice exhibited down‐regulated expression of TH as well as adrenergic signaling‐related genes.…”