Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons

Abstract

Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is altered in heart failure, and whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and proNGF immunoreactivity in CG neurons in heart failure rats following chronic coronary artery ligation was investigated. NGF immunoreactivity was decreased significantly in heart failure rats compared to sham-operated animals, whereas proNGF expression was unchanged. Changes in neurochemistry of CG neurons included attenuated expression of the cholinergic marker vesicular acetylcholine transporter, and increased expression of the neuropeptide vasoactive intestinal polypeptide. To further investigate norepinephrine’s role in promoting NGF synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists. An 82% increase in NGF mRNA levels was detected after 1hr of isoproterenol (β-AR agonist) treatment, which increased an additional 22% at 24hr. Antagonist treatment blocked isoproterenol-induced increases in NGF transcripts. In contrast, the α-AR agonist phenylephrine did not alter NGF mRNA expression. These results are consistent with β-AR mediated maintenance of NGF synthesis in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may potentially contribute to reduced connections with adjacent sympathetic nerves.

Endocardial Endothelial Dysfunction Progressively Disrupts Initially Anti then Pro-Thrombotic Pathways in Heart Failure Mice

“…Images were visualized with a confocal microscope (Nikon A1R) with orthogonal projection of z-stack images carried out with NIS Elements software (Nikon Instruments, Melville, NY). Quantitation of vWF immunostaining was carried out with ImageJ (NIH); threshold discrimination for staining area expressed relative to total sectional area [ 31 , 32 ].…”

“…To extract RNA from the endocardial surface, LV halves (n = 5–7 per group) were placed over a modified 384-well plate (as above) and incubated with Trizol reagent (100 μL, 15 min, Life Technologies, Grand Island, NY) followed by a standard chloroform-ethanol extraction and purification (RNA Clean, Zymo Research, Irvine, CA) [ 31 ]. 15 min Trizol reagent incubation of the LV endocardial surface was chosen; this time frame gave the highest yield of RNA that was positive for CD31 as an endothelial marker and negative for the cardiomyocyte marker cardiac beta-myosin heavy chain.…”

“…Manufacturer certified Taqman probe/primer sets were to TM (Mm00437014), EPCR (Mm00440992), vWF (Mm00550376), protein S (Mm0134326), and to two housekeeping genes; CD31 (Mm01242584) and Polr2a (Mm00839493). Data are expressed as a delta change in Ct expression from that of the housekeeping gene Polr2a [ 31 ].…”

Triactome: Neuro–Immune–Adipose Interactions. Implication in Vascular Biology

“…(35, 60), also see Ref. (14, 30, 34, 61)]. The expression of NGF and its receptor p75 NTR in the surrounding subEAT (coronary tunica adiposa ) has been examined simultaneously [Ref.…”

Studying the pathophysiologic connection between cardiovascular and nervous systems using stem cells

“…For instance, cardiac glial cell line–derived neurotrophic factor and neurturin play a role in the survival of parasympathetic neurons, while nerve growth factor and Neurotrophin‐3 are essential for the survival and outgrowth of sympathetic axons (Landis and Keefe, ; Kobayashi and Matsuoka, ; Glebova and Ginty, ; Mabe and Hoover, ; Fu et al, ; Simpson et al, ; Downs et al, ). Furthermore, cardiac neurotrophic factors regulate synaptic transmission, as well as neurotransmitter phenotype, of the postganglionic sympathetic neurons (Wyatt et al, ; Luther and Birren ; Hasan and Smith, ). Given the fact that circulating nerve growth factor levels dramatically increase after atrial fibrillation and myocardial injury and lead to sympathetic nerve sprouting (Meloni et al, ; Saygili et al, ; Hu et al, ), the embryonically established reciprocal relationship between the cardiac tissue and the innervating peripheral nervous system appears to be preserved throughout life.…”