Gender-modulated endogenous baseline neuropeptide Y Y1-receptor activation in the hindlimb of Sprague-Dawley rats

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.

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Auricular acupuncture decreases neuropeptide Y expression in the hypothalamus of food-deprived Sprague–Dawley rats

Neuroscience Letters ◽

10.1016/s0304-3940(01)01948-6 ◽

2001 ◽

Vol 307 (2) ◽

pp. 113-116 ◽

Cited By ~ 11

Author(s):

Ee-Hwa Kim ◽

Younhee Kim ◽

Mi-Hyun Jang ◽

Baek-Vin Lim ◽

Youn-Jung Kim ◽

...

Keyword(s):

Neuropeptide Y ◽

Auricular Acupuncture ◽

Sprague Dawley ◽

Sprague Dawley Rats

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Selected Contribution: Phrenic long-term facilitation requires 5-HT receptor activation during but not following episodic hypoxia

Journal of Applied Physiology ◽

10.1152/jappl.2001.90.5.2001 ◽

2001 ◽

Vol 90 (5) ◽

pp. 2001-2006 ◽

Cited By ~ 137

Author(s):

D. D. Fuller ◽

A. G. Zabka ◽

T. L. Baker ◽

G. S. Mitchell

Keyword(s):

Receptor Antagonist ◽

Phrenic Nerve ◽

Receptor Activation ◽

Sprague Dawley ◽

Nerve Activity ◽

Sprague Dawley Rats ◽

Episodic Hypoxia ◽

Baseline Levels ◽

Long Term Facilitation

Episodic hypoxia evokes a sustained augmentation of respiratory motor output known as long-term facilitation (LTF). Phrenic LTF is prevented by pretreatment with the 5-hydroxytryptamine (5-HT) receptor antagonist ketanserin. We tested the hypothesis that 5-HT receptor activation is necessary for the induction but not maintenance of phrenic LTF. Peak integrated phrenic nerve activity (∫Phr) was monitored for 1 h after three 5-min episodes of isocapnic hypoxia (arterial Po 2 = 40 ± 2 Torr; 5-min hyperoxic intervals) in four groups of anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats [ 1) control ( n = 11), 2) ketanserin pretreatment (2 mg/kg iv; n = 7), and ketanserin treatment 0 and 45 min after episodic hypoxia ( n = 7 each)]. Ketanserin transiently decreased ∫Phr, but it returned to baseline levels within 10 min. One hour after episodic hypoxia, ∫Phr was significantly elevated from baseline in control and in the 0- and 45-min posthypoxia ketanserin groups. Conversely, ketanserin pretreatment abolished phrenic LTF. We conclude that 5-HT receptor activation is necessary to initiate (during hypoxia) but not maintain (following hypoxia) phrenic LTF.

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Gastric leptin: a novel role in cardiovascular regulation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00997.2009 ◽

2010 ◽

Vol 298 (2) ◽

pp. H406-H414 ◽

Cited By ~ 16

Author(s):

D. M. Sartor ◽

A. J. M. Verberne

Keyword(s):

Cardiovascular Effects ◽

Receptor Activation ◽

Cardiovascular Regulation ◽

Sprague Dawley ◽

Inhibitory Effects ◽

Short Term ◽

Sprague Dawley Rats ◽

Gut Hormone ◽

Cervical Vagotomy ◽

Nerve Discharge

Gastric-derived leptin affects satiety and gastrointestinal function via vagal mechanisms and has been shown to interact with the gut hormone cholecystokinin (CCK). CCK selectively inhibits splanchnic sympathetic nerve discharge (SND) and the activity of a subset of presympathetic vasomotor neurons in the rostroventrolateral medulla (RVLM). The present study sought to examine the effects of gastric leptin on arterial pressure (AP), heart rate (HR), SND, and RVLM neuronal activity to determine whether its effects on cardiovascular regulation are dependent on CCK1 receptors and vagal afferent transmission. To mimic gastric leptin, leptin (15–30 μg/kg) was administered close to the coeliac artery in anesthetized, artificially ventilated Sprague-Dawley rats. Within 5 min, leptin selectively decreased the activity of RVLM neurons also inhibited by CCK (−27 ± 4%; P < 0.001; n = 15); these inhibitory effects were abolished following administration of the CCK1 receptor antagonist lorglumide. Leptin significantly decreased AP and HR (−10 ± 2 mmHg, P < 0.001; and −8 ± 2 beats/min, P < 0.01; n = 35) compared with saline (−1 ± 2 mmHg, 3 ± 2 beats/min; n = 30). In separate experiments, leptin inhibited splanchnic SND compared with saline (−9 ± 2% vs. 2 ± 3%, P < 0.01; n = 8). Bilateral cervical vagotomy abolished the sympathoinhibitory, hypotensive, and bradycardic effects of leptin ( P < 0.05; n = 6). Our results suggest that gastric leptin may exert acute sympathoinhibitory and cardiovascular effects via vagal transmission and CCK1 receptor activation and may play a separate role to adipose leptin in short-term cardiovascular regulation.

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Sympathetic and parasympathetic component of bradycardia triggered by stimulation of NTS P2X receptors

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00889.2005 ◽

2006 ◽

Vol 290 (2) ◽

pp. H807-H812 ◽

Cited By ~ 8

Author(s):

Amy M. Kitchen ◽

Donal S. O'Leary ◽

Tadeusz J. Scislo

Keyword(s):

Low Dose ◽

Nucleus Tractus Solitarius ◽

Receptor Activation ◽

P2x Receptors ◽

P2x Receptor ◽

High Dose ◽

Adrenergic Blockade ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Stimulation Of

We have previously shown that activation of P2X purinoceptors in the subpostremal nucleus tractus solitarius (NTS) produces a rapid bradycardia and hypotension. This bradycardia could occur via sympathetic withdrawal, parasympathetic activation, or a combination of both mechanisms. Thus we investigated the relative roles of parasympathetic activation and sympathetic withdrawal in mediating this bradycardia in chloralose-urethane anesthetized male Sprague-Dawley rats. Microinjections of the selective P2X purinoceptor agonist α,β-methylene ATP (25 pmol/50 nl and 100 pmol/50 nl) were made into the subpostremal NTS in control animals, after atenolol (2 mg/kg iv), a β1-selective antagonist, and after atropine methyl bromide (2 mg/kg iv), a muscarinic receptor antagonist. The bradycardia observed with activation of P2X receptors at the low dose of the agonist is mediated almost entirely by sympathetic withdrawal. After β1-adrenergic blockade, the bradycardia was reduced to just −5.1 ± 0.5 versus −28.8 ± 5.1 beats/min in intact animals. Muscarinic blockade did not produce any significant change in the bradycardic response at the low dose. At the high dose, both β1-adrenergic blockade and muscarinic blockade attenuated the bradycardia similarly, −37.4 ± 6.4 and −40.6 ± 3.7 beats/min, respectively, compared with −88.0 ± 11 beats/min in control animals. Double blockade of both β1-adrenergic and muscarinic receptors virtually abolished the response (−2.5 ± 0.8 beats/min). We conclude that the relative contributions of parasympathetic activation and sympathetic withdrawal are dependent on the extent of P2X receptor activation.

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Up-regulation of Neuropeptide Y Receptors in the Hypothalamus of Monosodium Glutamate-lesioned Sprague-Dawley Rats

Nutritional Neuroscience ◽

10.1080/10284150412331281040 ◽

2004 ◽

Vol 7 (4) ◽

pp. 241-245 ◽

Cited By ~ 12

Author(s):

A. Stricker-Krongrad ◽

B. Beck

Keyword(s):

Neuropeptide Y ◽

Monosodium Glutamate ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Y Receptors ◽

Neuropeptide Y Receptors

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Abstract 386: Compound 21 Induces Natriuresis via Renal AT2 Receptor Activation in Male and Female Rats

Hypertension ◽

10.1161/hyp.60.suppl_1.a386 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Brandon A Kemp ◽

Nancy L Howell ◽

Robert M Carey

Keyword(s):

Receptor Activation ◽

Female Rats ◽

Male Rats ◽

Sprague Dawley ◽

Male And Female ◽

Male And Female Rats ◽

Sprague Dawley Rats ◽

Angiotensin Iii ◽

Compound 21 ◽

Renal Cortical Interstitium

Endogenous renal des-aspartyl 1 -angiotensin II (angiotensin III) activates renal proximal tubule AT 2 receptors (AT 2 Rs) and induces natriuresis via a nitric oxide-cyclic GMP signaling pathway. The present study explores the ability of highly selective non-peptide AT 2 R agonist Compound 21 (C21) to induce natriuresis. Sprague-Dawley rats (12 weeks old; male N=22; female N=18) were studied in the presence and absence of concurrent 24-h AT 1 R blockade with candesartan (CAND;0.01 mg/kg/min). Rats were anesthetized with Inactin 100 mg/kg i.p., uninephrectomized and instrumented for delivery of 3 cumulative 30-min i.v. infusions of C21 (100, 200, and 300 ng/kg/min) following a 30-min control infusion of vehicle. Mean arterial pressure (MAP) was measured for all periods and urine Na + excretion rate (U Na V) was calculated for the control and final C21 collection periods. To determine whether the systemically induced natriuresis is mediated by renal AT 2 Rs, PD-123319 (PD), a specific AT 2 R antagonist, was infused directly into the renal cortical interstitium(20 μg/kg/min and 10 μg/kg/min for females and males, respectively) during the i.v. C21 infusions. In female rats, C21 increased U Na V from 1.5 ± 0.20 to 7.48 ± 0.95 μmol/min (P<0.0001). This response was abrogated by concurrent intrarenal PD infusion [control 0.74 ± 0.19 vs. C21 2.02 ± 0.50 μmol/min (P<0.001from C21 alone). Systemic CAND administration augmented the natriuretic response to C21 [control 1.29 ± 0.25 vs. C21 10.68 ± 0.70 μmol/min (P<0.05 from C21 alone)]. In male rats, C21 increased U Na V from 0.46 ±0.08 to 6.21 ± 1.33 μmol/min (P<0.01). This response was blocked by concurrent intrarenal PD infusion [control 0.39 ± 0.11 vs. C21 1.69 ± 0.53 μmol/min (P<0.05 from C21 alone). Systemic CAND did not significantly alter the natriuretic response to C21 alone [control 0.49 ± 0.15 vs. C21 7.67 ± 0.72 μmol/min (P = NS from C21 alone). In female rats, CAND augmented the natriuretic response to C21 over that of male rats (P<0.01). Systemic arterial pressures were decreased by CAND in both male and female rats but were unchanged by C21 alone or together with intrarenal PD. C21 induces natriuresis via renal AT 2 R activation in both male and female rats. These data suggest the potential for AT 2 R agonist therapy in hypertension.

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Postnatal intracerebroventricular exposure to neuropeptide Y causes weight loss in female adult rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00557.2001 ◽

2003 ◽

Vol 284 (6) ◽

pp. R1560-R1566 ◽

Cited By ~ 14

Author(s):

Amit Varma ◽

Jing He ◽

Lisa Weissfeld ◽

Sherin U. Devaskar

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Neuropeptide Y ◽

Body Weight Gain ◽

Sprague Dawley ◽

Adult Rats ◽

Sprague Dawley Rats ◽

Old Adult ◽

Arcuate Nuclei

We investigated the effect of repetitive postnatal (2–7 days) intracerebroventricular administration of neuropeptide Y (NPY) on food intake and body weight gain in the 3- to 120-day-old Sprague-Dawley rats. NPY caused a 32% transient increase in body weight gain with elevated circulating insulin concentrations within 24 h. This early intervention led to the persistence of hyperinsulinemia and relative hyperleptinemia with euglycemia in the 120-day-old female alone. This perturbation was associated with 50% suppression in adult female hypothalamic NPY concentrations and a 50–85% decline in NPY immunoreactivity in the paraventricular and arcuate nuclei. This change was paralleled by a ∼20% decline in food intake and body weight gain at 60 and 120 days. However, when exogenous NPY was stereotaxically reinjected into the paraventricular nucleus of the ∼120-day-old adult females who were pretreated with NPY postnatally, an increase in food intake and body weight gain was noted, attesting to no disruption in the NPY end-organ responsivity. We conclude that postnatal intracerebroventricular NPY has long-lasting effects that predetermine the resultant adult phenotype in a sex-specific manner.

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Anxiety responses and neurochemical changes in a kaolin-induced rat model of hydrocephalus

Journal of Neurosurgery Pediatrics ◽

10.3171/2011.1.peds10182 ◽

2011 ◽

Vol 7 (4) ◽

pp. 401-407 ◽

Cited By ~ 5

Author(s):

Yong Sup Hwang ◽

Insop Shim ◽

Jin Woo Chang

Keyword(s):

Neuropeptide Y ◽

Rat Model ◽

Elevated Plus Maze ◽

Sprague Dawley ◽

Injection Group ◽

Abnormal Gait ◽

Sprague Dawley Rats ◽

Plus Maze ◽

Anxiety Response ◽

Neurochemical Changes

Object Hydrocephalus is a pathological enlargement of the ventricles of the brain, which can result from various diseases of the central nervous system. Patients with hydrocephalus frequently show motor abnormalities, such as abnormal gait and posture, as well as intellectual and emotional impairment. The present study was designed to investigate anxiety responses in rats with kaolin-induced hydrocephalus. Methods A total of 26 Sprague-Dawley rats were used for this study. Hydrocephalus was induced in 14 Sprague-Dawley rats by injecting 0.1 ml of 20% kaolin solution into the cisterna magna; 12 rats were administered the same volume of saline in the same fashion and served as controls. Seven of the rats that were injected with kaolin and 6 of the rats injected with saline were killed 3 days after injection (Group 1); the remaining rats were killed 4 weeks after injection (Group 2) to evaluate effects related to acute and chronic hydrocephalus. The rats were tested in an elevated plus maze after induction of hydrocephalus by kaolin injection. After the animals were killed, brain sections were immunostained for cholecystokinin and neuropeptide Y. In addition, tyrosine hydroxlyase immunoreactivity in the ventral tegmental area was evaluated by immunohistological staining. Results The rats with acute hydrocephalus showed decreased entry into and spent less time in the open arms of the elevated plus maze as compared with the control rats. The hydrocephalic rats had significantly more cholecystokinin-immunoreactive neurons and fewer neuropeptide Y–immunoreactive neurons in their brains. In addition, hydrocephalus progress in this model was positively correlated with the anxiety response. The numbers of tyrosine hydroxlyase–immunoreactive neurons were decreased significantly in the hydrocephalic rats as compared with the control rats. Conclusions These results suggest that the rat model of hydrocephalus is characterized by increased anxiety response and is associated with the functional impairment of the central dopamine system.

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