Norepinephrine Release In Rats Research Articles

Inhibition of nicotine-induced hippocampal norepinephrine release in rats by alpha-conotoxins MII and AuIB microinjected into the locus coeruleus

Hippocampal norepinephrine (NE) is secreted by neurons projecting from the locus coeruleus (LC) to the hippocampus; LC nicotinic receptors (NAchRs) are involved in the effects of systemic nicotine on this pathway. To clarify the NAchR subtypes, NAchR antagonists, termed α-conotoxins, were microinjected into the LC before nicotine; MII and AulB were used to assess the potential involvement of α3 β2 and α3 β4 subunit-containing NAchRs, respectively. Nicotine dose-dependently stimulated hippocampal NE release ( P<0.01). MII (>0.25 pmol) reduced the NE response to nicotine (67% decrease; P<0.05), as did AuIB (44% reduction by 25 pmol; P<0.05). Administered together, however, MII and AuIB were no more effective than MII. Thus, MII and AuIB are capable of interacting with NAchR subtypes other than those previously defined as α3 β2 and α3 β4, respectively. NAchRs containing both β2 and β4subunits may be involved.

Hypothalamic changes in norepinephrine release in rats with estradiol valerate-induced polycystic ovaries.

Chronic anovulation and polycystic ovaries (PCO) can be induced by a single i.m. injection of estradiol valerate (EV, 2 mg in oil) in the rat. Constant exposure to high plasma levels of estradiol provokes a neurotoxic effect on the hypothalamic neurons, including those from the arcuate nucleus. Because of the important participation of hypothalamic norepinephrine (NE) in the regulation of GnRH release and the possible noxious effect of prolonged exposure of these neurons to estradiol, our interest was to study the activity of the noradrenergic neurons innervating the hypothalamus. We analyzed the biosynthesis, content, and release of NE from the noradrenergic nerve terminals of the hypothalamus during the PCO condition. We found a decrease in tyrosine hydroxylase (TH) activity and in the content of dopamine (DA) in the anterior hypothalamus after 2 mo of EV injection, whereas dopamine-beta-hydroxylase (D beta H) was increased without changes in NE content. No variations in TH activity or in DA and NE contents in the medial hypothalamus were observed, but a decrease in D beta H activity was evident. After 2 mo of EV administration, an increase in the electrically induced release of NE from anterior hypothalamic blocks incubated in vitro was detected; this effect was not evidenced in the medial hypothalamus. After 5 mo of EV administration, release of NE increased in anterior hypothalamic blocks but decreased in medial hypothalamic tissue. The inhibitory effect of morphine on NE release found in control animals was increased in the hypothalamus from PCO rats, suggesting an increased number of mu-opioid binding sites in noradrenergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II and Noradrenergic Transmission in the Pithed Rat

The norepinephrine (NE) release rate, determined in the pithed rat with stimulated sympathetic outflow (3 Hz), was calculated from the steady-state concentrations of endogenous NE and [3H]NE in the central venous pool after infusion of [3H]NE intraarterially (i.a.). This technique appropriately corrects for NE metabolism and disposition since the [3H]NE closely follows the removal path of neuronally released NE. Infusion of angiotensin II (AII) [0.1 microgram/kg/min, intravenously (i.v.)] failed to increase the NE release rate. A higher rate of infusion of AII (1.0 microgram/kg/min, i.v.) markedly increased the NE release rate. The converting enzyme inhibitor captopril (1 mg/kg, i.v.) and the AII-receptor blocking drug saralasin (10 micrograms/kg/min, i.v.) decreased the NE release rate, indicating a tonic activation of facilitatory prejunctional AII receptors at sympathetic nerve endings. After bilateral nephrectomy, captopril and saralasin did not decrease the NE release rate. This suggests that renin release from the kidney is the primary determinant of AII effects and that local tissue generation of AII is not important Other differences were observed in nephrectomized rats: AII (0.1 microgram/kg/min, i.v.), in contrast to its lack of effect in rats with kidneys, increased the NE release rate. This suggests that the lack of effect of AII (0.1 microgram/kg/min, i.v.) on NE release in rats with kidneys may occur because facilitatory prejunctional AII receptors are maximally activated by endogenous AII.

Renal sympathetic nerve activity and norepinephrine release in rats.

We examined relationships between changes in directly recorded renal sympathetic nerve activity (RSNA) and renal and total body spillover of norepinephrine into the bloodstream (RNEs and TBNEs, respectively) in anesthetized, adrenal-demedullated rats. Intravenous infusions of nitroprusside (NP) or phenylephrine (PH) produced reflexive, dose-dependent changes in RSNA. High-doses of NP significantly increased RSNA by 90%, RNEs by 155%, and TBNEs by 268%. High doses of PH significantly decreased RSNA by 37%, RNEs by 35%, and TBNEs by 33%. Ganglionic blockade with chlorisondamine decreased RSNA by 65% (P less than 0.05), RNEs by 10%, and TBNEs by 51% (P less than 0.05). There was a significant curvilinear relationship between mean changes in RSNA and mean changes in RNEs (r = 0.99). Simultaneous in vivo measurement of sympathetic nerve traffic and regional release of norepinephrine therefore may be useful in the assessment of presynaptic actions of drugs and hormones and in the evaluation of abnormal sympathetic neurotransmission in disease states.