Alterations in Sympathetic Ganglionic Transmission in Response to Angiotensin II in (mRen2)27 Transgenic Rats

Abstract

Abstract-Hypertension in (mRen2)27 transgenic rats is partly dependent on activation of the sympathetic nervous system, but the role of ganglionic transmission is unknown. We assessed indices of synaptic plasticity (post-tetanic short-term potentiation [PTP] and long-term potentiation [LTP]) and sympathetic ganglionic transmission without tetany in superior cervical ganglia (SCG) of Hannover Sprague-Dawley rats (HnSD) versus (mRen2)27 rats. Key Words: angiotensin II Ⅲ rats, transgenic Ⅲ autonomic nervous system Ⅲ hypertension Ⅲ arterial Ⅲ receptors I n the mammalian autonomic ganglia, post-tetanic potentiation (PTP) and long-term potentiation (LTP) of synaptic transmission are examples of activity-dependent forms of synaptic plasticity. A few seconds of repetitive presynaptic stimulation producing profound changes in the efficacy of chemical synaptic transmission that can last for seconds or minutes is designated PTP, whereas increased synaptic strength persisting for hours or days is termed LTP. Activitydependent LTP is dependent on activation of serotonin 5-HT 3 receptors in rat superior cervical ganglia (SCG) 1 and is independent of activation of either cholinergic or adrenergic receptors 2,3 in rats. In addition to activity-dependent mechanisms, enduring changes in the synaptic strength also occur through activity-independent mechanisms. For example, specific antigen challenges of isolated sympathetic ganglia activates resident mast cells to release substances that initiate long-lasting increases in synaptic efficacy. 4 Also, application of exogenous catecholamines induces LTP of cholinergic 5 or peptidergic synaptic transmission in sympathetic ganglia. 6 Although the role of ganglionic LTP in the physiology of autonomic ganglia is not understood, recent reports show a positive relationship between ganglionic LTP and blood pressure in ouabain-dependent hypertension that favors the possibility that ganglionic LTP contributes to increased sympathetic nerve activity (SNA) in hypertension or vice versa. 7 Captopril reversed both hypertension and ganglionic abnormalities, suggesting a role for angiotensin (Ang) II in an ouabain-dependent model of hypertension. Other studies show alterations in ganglionic function in spontaneously hypertensive rats (SHRs). 8,9 For example, postsynaptic spike frequency adaptation is curtailed in SHRs. 9 Presynaptically, there is enhanced release of acetylcholine. 10 Collectively, these changes in ganglionic function may contribute to increased SNA in the development and maintenance of hypertension observed in human and experimental hypertension. 11,[12][13][14][15][16][17][18][19] However, less well understood is how enhanced SNA contributes to elevated blood pressure or alters ganglionic synaptic plasticity. In the ouabain-dependent rat, SHRs, and renin-transgenic rat, Ang II acting centrally to increase sympathetic nervous system (SNS) outflow appears to be a common feature; but increased peripheral levels of Ang II, or local increases in the peptide, cannot be excluded. In fact,

Neuroendocrine profiling in inherited stress-induced arterial hypertension rat strain with stress-sensitive arterial hypertension

“…Many researchers have described the involvement of the neuroendocrine, particularly of the sympathetic adrenal medullary mechanisms, in the formation of arterial hypertension in human (Mancia et al 1997, Williams 1997, Sharma et al 1998, DeQuattro & Feng 2002, DiBona 2004. The sympathetic-dependent changes in the kidney function would contribute additionally to the pathogenesis and progression of the hypertensive disease (Schneider et al 2001, Aileru et al 2004, Grisk 2004, Schlaich et al 2004.…”

Increased plasma angiotensin II in postural tachycardia syndrome (POTS) is related to reduced blood flow and blood volume

“…In addition, Ang II can exert potent indirect effects on vasoconstriction through its potentiating effects on the sympathetic nervous system [40]. Specifically, Ang II can increase the release of noradrenaline (norepinephrine) from ganglionic [41] and postganglionic [42] sympathetic nerves. Also, importantly, Ang II promotes oxidative stress [43][44][45] by causing the formation of superoxide radical through its effects on NADPH oxidase [43].…”

Angiotensin-(1-7) and Baroreflex Function in Nucleus Tractus Solitarii of (mRen2)27 Transgenic Rats

“…The sections were then incubated with 0.35 nM 125 I-Sarthran in the same buffer in the presence or absence of 10 μM (D-Ala 7 )-Ang-(1−7) to determine whether this antagonist competes for binding in the nTS as compared with losartan (3 μM) for AT 1 receptors or PD123319 (3 μM) for AT 2 receptors. 17,28,29 Slides were rinsed and dried according to published protocols, placed against x-ray film (Kodak Biomax MR Scientific Imaging film, Kodak, Rochester, NY) in cassettes for 6 to 9 days with 14 C standards. Film images in the combined region of the nTS and dmnX of the dorsal medulla were analyzed by computerized densitometry at two rostro-caudal levels.…”