Endorphinergic mechanism in the central cardiovascular and analgesic effects of clonidine

1987 ◽  
Vol 65 (8) ◽  
pp. 1624-1632 ◽  
Author(s):  
G. Kunos ◽  
R. Mosqueda-Garcia ◽  
J. A. Mastrianni ◽  
F. V. Abbott
Keyword(s):  
Receptor Antagonist ◽  
Arcuate Nucleus ◽  
Monosodium Glutamate ◽  
Opiate Receptors ◽  
Cardiovascular Effects ◽  
Male Rats ◽  
Sprague Dawley ◽  
Wky Rats ◽  
Sd Rats ◽  
Wistar Kyoto

In urethane-anesthetized male rats, injection of 5 nmol clonidine into the nucleus of the solitary tract (NTS) causes hypotension and bradycardia. These effects are greater in spontaneously hypertensive rats (SHR) and normotensive Sprague–Dawley (SD) rats than in normotensive Wistar–Kyoto (WKY) rats. The effects of clonidine are stereoselectively inhibited by 100 ng intra-NTS naloxone in SHR and SD but not in WKY rats. In SHR, the effects of clonidine are also inhibited by intra-NTS administration of ICI 174864 (a δ-receptor antagonist) but not by β-funaltrexamine (a μ-receptor antagonist), while in SD rats only the μ- and not the δ-antagonist was effective. Neonatal treatment of SHR with monosodium glutamate (MSG) reduced the β-endorphin content of the arcuate nucleus and the NTS, reduced the cardiovascular effects of clonidine, and abolished their naloxone sensitivity. MSG treatment of newborn WKY reduced the β-endorphin content of the arcuate nucleus but not the NTS and did not affect the responses to clonidine. Measurement of pain sensitivity by the formalin test indicated that clonidine was more potent as an analgesic in SHR and SD than in WKY rats, and its effect was inhibited by naloxone (2 mg/kg i.p.) in the former two strains but not in WKY. It is proposed that a naloxone-sensitive component of the cardiovascular effects of clonidine is due to release of a β-endorphin-like opioid from the NTS, and that this mechanism is present in SHR and SD but not in WKY rats. The opiate receptors mediating the effects of the opioid appear to be of the μ-subtype in SD rats and of the δ-subtype in SHR. The results also support a close relationship between central cardiovascular and pain regulatory mechanisms.

Distribution of kallikrein-binding protein mRNA in kidneys and difference between SHR and WKY rats

1994 ◽  
Vol 267 (2) ◽  
pp. F325-F330 ◽  
Author(s):  
T. Yang ◽  
Y. Terada ◽  
H. Nonoguchi ◽  
M. Tsujino ◽  
K. Tomita ◽  
...  
Keyword(s):  
Blot Analysis ◽  
Binding Protein ◽  
Collecting Duct ◽  
Cortical Collecting Duct ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Sd Rats ◽  
Medullary Collecting Duct ◽  
Wistar Kyoto

We investigated kallikrein-binding protein (KBP) mRNA distribution in the kidney of Sprague-Dawley (SD) rats, spontaneously hypertensive rats (SHR), and Wistar-Kyoto strain (WKY) rats. Northern blot analysis revealed that KBP mRNA was located mainly in the medulla and with lower amounts in SHR than in WKY rats. KBP mRNA in microdissected nephron segments was detected by reverse transcription and polymerase chain reaction (RT-PCR) followed by Southern blot analysis. In SD rats, the most abundant signals were consistently found in inner medullary collecting duct (IMCD), with small amounts in outer medullary collecting duct, proximal convoluted tubule, and glomerulus. No signals were found in connecting tubule and cortical collecting duct. The nephron distribution of KBP mRNA was similar in WKY and SD rats. Only a small amount of signal was found, however, in IMCD of SHR. In conclusion, 1) KBP mRNA was predominantly distributed in the medullary segments of the distal nephron, downstream from the known kallikrein activity site in the collecting duct, and 2) KBP mRNA expression was significantly decreased in the kidney of SHR.

scholarly journals Exacerbated LPS/GalN-Induced Liver Injury in the Stress-Sensitive Wistar Kyoto Rat Is Associated with Changes in the Endocannabinoid System

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3834
Author(s):  
Marykate Killilea ◽  
Daniel M. Kerr ◽  
Beth M. Mallard ◽  
Michelle Roche ◽  
Antony M. Wheatley
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Endocannabinoid System ◽  
Hepatic Function ◽  
Receptor Expression ◽  
Sprague Dawley ◽  
Wky Rats ◽  
Sd Rats ◽  
Rat Strain ◽  
Wistar Kyoto

Acute liver injury (ALI) is a highly destructive and potentially life-threatening condition, exacerbated by physical and psychological stress. The endocannabinoid system plays a key role in modulating stress and hepatic function. The aim of this study was to examine the development of acute liver injury in the genetically susceptible stress-sensitive Wistar-Kyoto (WKY) rat compared with normo-stress-sensitive Sprague Dawley (SD) rats, and associated changes in the endocannabinoid system. Administration of the hepatotoxin lipopolysaccharide/D-Galactosamine (LPS/GalN) resulted in marked liver injury in WKY, but not SD rats, with increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) plasma levels, significant histopathological changes, increased hepatic pro-inflammatory cytokine expression and caspase-3 activity and expression and reduced Glutathione (GSH) activity. Furthermore, compared to SD controls, WKY rats display increased anandamide and 2-Arachidonoylglycerol levels concurrent with decreased expression of their metabolic enzymes and a decrease in cannabinoid (CB)1 receptor expression following LPS/GalN. CB1 antagonism with AM6545 or CB2 agonism with JWH133 did not alter LPS/GalN-induced liver injury in SD or WKY rats. These findings demonstrate exacerbation of acute liver injury induced by LPS/GalN in a stress-sensitive rat strain, with effects associated with alterations in the hepatic endocannabinoid system. Further studies are required to determine if the endocannabinoid system mediates or modulates the exacerbation of liver injury in this stress-sensitive rat strain.

Abstract P045: Sex And Age Specific Circulating Aldosterone Changes In Transgenic Hypertensive (mRen2)27 Rats And Hannover Sprague Dawley (SD) Rats And Its Association With Blood Pressure And Cardiac Function

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Fatima Ryalat ◽  
N Cruz-Diaz ◽  
W Graham ◽  
T Gwathmey-Williams ◽  
P E Gallagher ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Cardiac Function ◽  
Target Organ Damage ◽  
Aging Effect ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Aldosterone Antagonists ◽  
Sd Rats

Aldosterone plays a significant role in hypertension and target organ damage. Aldosterone antagonists are used in the management of heart failure. However, neither the influence of age nor sex on aldosterone pathophysiology is well understood. We investigated the changes in circulating aldosterone with age and its association with cardiovascular function, using male and female hypertensive renin transgenic (mRen2)27 rats and SD rats at 20 and 50 weeks of age. Both male (22 ± 3 vs. 12 ± 2 ng/dL, n = 9 - 12, p < 0.05) and female (59 ± 10 vs. 23 ± 8 ng/dL, n = 6 - 10, p < 0.05) hypertensive rats had higher serum aldosterone compared with SD rats at 20 weeks of age. At 50 weeks of age, the difference persisted in the hypertensive female rats (63 ± 8 vs. SD: 33 ± 7 ng/dL, n = 6 - 7, p < 0.05), but not in the males. SD male rats have higher systolic blood pressure (SBP) as they age, and consequently develop cardiac diastolic dysfunction associated with higher aldosterone at 50 weeks compared to 20 weeks (28 ± 3 vs. 12 ± 2 ng/dL, n = 7 - 9, p < 0.05). This aging effect on aldosterone was not significant in the other groups. We showed previously that SD males treated with polyphenol rich muscadine grape extract (MGE) have lower aldosterone, less aortic stiffness and better cardiac diastolic function (E/e’) than controls at the older age; the MGE effect was not seen in (mRen2)27 males. Sex differences in aldosterone were not significant in the SD rats at either time point. However, (mRen2)27 female rats had higher aldosterone than (mRen2)27 males at both 20 weeks (59 ± 10 vs. 22 ± 3 ng/dL, n = 10 - 12, p < 0.05) and 50 weeks (63 ± 8 vs. 31 ± 7 ng/dL, n = 6 - 7, p < 0.05), despite the lack of significant differences in SBP. (mRen2)27 female rats preserve cardiac function better than males throughout their life span, while males develop indices of heart failure. Our data suggest that lower aldosterone levels in hypertensive males compared with females do not protect against the higher lifetime burden of elevated SBP and also may reflect different mechanisms controlling circulating aldosterone between sexes. In addition, data suggest a potential therapeutic effect of MGE in the management of age-associated moderate hypertension.

Neurons from neonatal hypertensive rats exhibit abnormal membrane properties in vitro

1990 ◽  
Vol 259 (3) ◽  
pp. C389-C396 ◽  
Author(s):  
B. C. Jubelin ◽  
M. S. Kannan
Keyword(s):  
Action Potentials ◽  
Membrane Properties ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Enzymatic Dissociation ◽  
Sd Rats ◽  
High Calcium ◽  
Cervical Ganglia ◽  
Wistar Kyoto

The in vitro membrane properties of neurons from superior cervical ganglia (SCG) of neonatal spontaneously hypertensive (SH), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats were studied with microelectrodes. Neurons were obtained by enzymatic dissociation, plated, irradiated, and studied after 2-5 wk. Most SH neurons showed multiple action potentials in response to an intracellular long-duration depolarizing pulse (multiple firing), whereas most neurons from WKY or SD rats generated only one or two action potentials. Multiple firing was inhibited by low concentrations of cobalt (10(-5) M) but not by tetrodotoxin (TTX) (3 x 10(-6) M). Neither high calcium (5-10 x 10(-3) M) nor the Ca2+(-)channel opener BAY K 8644 (10(-6) M) could induce multiple firing in SD or WKY neurons. However, multiple firing was readily induced by apamin (10(-6) M) or tetraethylammonium chloride (5 x 10(-3) M) (Ca2+(-)activated K+(-)channels blockers), with cobalt and TTX sensitivities similar to native multiple-firing neurons. We conclude that 1) multiple firing is characteristic of neonate SH rats SCG neurons in vitro and depends on regenerative Ca2+ currents; 2) multiple firing in SH neurons results from a lack of activation of a Ca2+(-)activated K+ conductance and not from a lack of internal Ca2+ availability; and 3) multiple firing in SCG neurons mirrors a default in K+ conductance common to all cells in genetically hypertensive individuals.

Long-term captopril treatment restores natriuresis after carotid baroreceptor activation in the SHR

1997 ◽  
Vol 273 (1) ◽  
pp. R70-R79
Author(s):  
J. P. Valentin ◽  
S. A. Mazbar ◽  
M. H. Humphreys
Keyword(s):  
Renal Plasma Flow ◽  
Renal Nerves ◽  
Sprague Dawley ◽  
Wky Rats ◽  
Sprague Dawley Rats ◽  
Long Term Treatment ◽  
Bilateral Carotid ◽  
Wistar Kyoto ◽  
Captopril Treatment

In anesthetized Sprague-Dawley rats, intermittent bilateral carotid artery traction (BilCAT) caused a transient decrease in mean arterial pressure (MAP) of 28 +/- 3 mmHg and led to a progressive increase in sodium excretion (UNaV) that nearly doubled 45-90 min after initiation of the repetitive application of BilCAT (P < 0.001). This natriuresis was accompanied by an increase in glomerular filtration rate (GFR) from 2.70 +/- 0.3 to 3.2 +/- 0.3 ml/min (P < 0.001), no change in renal plasma flow [clearance of p-aminohippurate (PAH)], and an increase in the fractional excretion of lithium. Rats with bilateral renal denervation exhibited neither natriuresis nor an increase in GFR in response to BilCAT despite similar vasodepression caused by the maneuver. Normotensive Wistar-Kyoto (WKY) rats responded to BilCAT like Sprague-Dawley rats, whereas spontaneously hypertensive rats (SHR) exhibited an exaggerated vasodepressor response to BilCAT (-51 +/- 3 mmHg) without increasing either UNaV or GFR. Separate groups of WKY and SHR were treated from 4 wk of age with captopril added to the drinking water at a concentration of 1 g/l. At 12-14 wk, both groups had lower MAP compared with untreated animals. Captopril treatment did not alter either the natriuretic response or the increase in GFR seen in untreated WKY after BilCAT, and the maneuver produced equivalent degrees of vasodepression as in controls. However, treated SHR now responded to BilCAT with increases in both UNaV and GFR that closely resembled the responses seen in Sprague-Dawley and WKY rats. These results suggest that BilCAT produces natriuresis through a pathway dependent on the renal nerves. This pathway does not function in untreated SHR despite similar vasodepression. Long-term treatment with captopril restores this reflex pathway in SHR, lending support to the concept that angiotensin II is critically linked to heightened sympathetic nerve activity and abnormal sodium metabolism in this strain.

scholarly journals Improved cardiovascular autonomic modulation in transgenic rats expressing an Ang-(1-7)-producing fusion protein

2017 ◽  
Vol 95 (9) ◽  
pp. 993-998 ◽  
Author(s):  
Daniela Ravizzoni Dartora ◽  
Maria-Claudia Irigoyen ◽  
Karina Rabello Casali ◽  
Ivana C. Moraes-Silva ◽  
Mariane Bertagnolli ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiovascular Effects ◽  
Chronic Administration ◽  
Acute Administration ◽  
Autonomic Modulation ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Sd Rats ◽  
Sympathetic Modulation ◽  
Acute Elevation

Angiotensin-(1-7) counterbalances angiotensin II cardiovascular effects. However, it has yet to be determined how cardiovascular autonomic modulation may be affected by chronic and acute elevation of Ang-(1-7). Hemodynamics and cardiovascular autonomic profile were evaluated in male Sprague-Dawley (SD) rats and transgenic rats (TGR) overexpressing Ang-(1-7) [TGR(A1-7)3292]. Blood pressure (BP) was directly measured while cardiovascular autonomic modulation was evaluated by spectral analysis. TGR received A-779 or vehicle and SD rats received Ang-(1-7) or vehicle and were monitored for 5 h after i.v. administration. In another set of experiments with TGR, A-779 was infused for 7 days using osmotic mini pumps. Although at baseline no differences were observed, acute administration of A-779 in TGR produced a marked long-lasting increase in BP accompanied by increased BP variability (BPV) and sympathetic modulation to the vessels. Likewise, chronic administration of A-779 with osmotic mini pumps in TGR increased heart rate, sympathovagal balance, BPV, and sympathetic modulation to the vessels. Administration of Ang-(1-7) to SD rats increased heart rate variability values in 88% accompanied by 8% of vagal modulation increase and 18% of mean BP reduction. These results show that both acute and chronic alteration in the Ang-(1-7)-Mas receptor axis may lead to important changes in the autonomic control of circulation, impacting either sympathetic and (or) parasympathetic systems.

scholarly journals Toxicological Features ofCatha edulis(Khat) on Livers and Kidneys of Male and Female Sprague-Dawley Rats: A Subchronic Study

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Abdulsamad Alsalahi ◽  
Mahmood Ameen Abdulla ◽  
Mohammed Al-Mamary ◽  
Mohamed Ibrahim Noordin ◽  
Siddig Ibrahim Abdelwahab ◽  
...  
Keyword(s):  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Catha Edulis ◽  
Male And Female ◽  
Sd Rats ◽  
Sprague Dawley Rats ◽  
Serum Aspartate Aminotransferase ◽  
Liver And Kidney ◽  
Kg Medium

Hepato- and nephrotoxicity of Khat consumption (Catha edulisForskal) have been evoked. Therefore, this study was conducted to evaluate such possible hepatorenal toxicity in female and male Sprague-Dawley rats (SD rats) focusing primarily on liver and kidney. In addition, female and male rats were investigated separately. Accordingly, forty-eight SD-rats (100–120 g) were distributed randomly into four groups of males and female (n=12). Normal controls (NCs) received distilled water, whereas test groups received 500 mg/kg (low dose (LD)), 1000 mg/kg (medium dose (MD)), or 2000 mg/kg (high dose (HD)) of crude extract ofCatha edulisorally for 4 weeks. Then, physical, biochemical, hematological, and histological parameters were analyzed. Results in Khat-fed rats showed hepatic enlargement, abnormal findings in serum aspartate aminotransferase (AST), and alkaline phosphatase (ALP) of male and female SD-rats and serum albumin (A) and serum creatinine (Cr) of female as compared to controls. In addition, histopathological abnormalities confirmed hepatic and renal toxicities of Khat that were related to heavy Khat consumption. In summary, Khat could be associated with hepatic hypertrophy and hepatotoxicity in male and female SD-rats and nephrotoxicity only in female SD-rats.

Activation of the central histaminergic system mediates arachidonic-acid-induced cardiovascular effects

2014 ◽  
Vol 92 (8) ◽  
pp. 645-654 ◽  
Author(s):  
Burcin Altinbas ◽  
Bora Burak Topuz ◽  
Tuncay İlhan ◽  
Mustafa Sertac Yilmaz ◽  
Hatice Erdost ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Receptor Antagonist ◽  
Cardiovascular Effects ◽  
Posterior Hypothalamus ◽  
Sprague Dawley ◽  
H2 Receptor Antagonist ◽  
Histaminergic System ◽  
Histaminergic Neurons ◽  
H4 Receptor ◽  
Cox 1

The aim of this study was to explain the involvement of the central histaminergic system in arachidonic acid (AA)-induced cardiovascular effects in normotensive rats using hemodynamic, immunohistochemistry, and microdialysis studies. Intracerebroventricularly (i.c.v.) administered AA (0.25, 0.5, and 1.0 μmol) induced dose- and time-dependent increases in mean arterial pressure and decreased heart rate in conscious normotensive Sprague–Dawley rats. Central injection of AA (0.5 μmol) also increased posterior hypothalamic extracellular histamine levels and produced strong COX-1 but not COX-2 immunoreactivity in the posterior hypothalamus of rats. Moreover, the cardiovascular effects and COX-1 immunoreactivity in the posterior hypothalamus induced by AA (0.5 μmol; i.c.v.) were almost completely blocked by the H2 receptor antagonist ranitidine (50 and 100 nmol; i.c.v.) and partially blocked by the H1 receptor blocker chlorpheniramine (100 nmol; i.c.v.) and the H3–H4 receptor antagonist thioperamide (50 and 100 nmol; i.c.v.). In conclusion, these results indicate that centrally administered AA induces pressor and bradycardic responses in conscious rats. Moreover, we suggest that AA may activate histaminergic neurons and increase extracellular histamine levels, particularly in the posterior hypothalamus. Acting as a neurotransmitter, histamine is potentially involved in AA-induced cardiovascular effects under normotensive conditions.

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