Furosemide inhibits the centrally‐mediated pressor response to clonidine in conscious, normotensive rats

Kawasaki, Hiromu; Nakamura, Shigeru; Takasaki, Koichiro

doi:10.1111/j.1476-5381.1991.tb12480.x

Cited by 7 publications

(8 citation statements)

References 14 publications

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“…These results are consisitent with our previous reports that the clonidine-induced pressor re sponse was abolished by 48 hours of water deprivation (4) and by furosemide (5). Inasmuch as the inhibitory effect of furosemide was correlated with increased urine volume, we proposed that the inhibition is associated with loss of body fluid volume (5). The present finding that clonidine causes a marked depressor response in WKY and SHR pretreated with furosemide, and in those deprived of water, is also consistent with our pre vious reports of a depressor response to clonidine in water-deprived or furosemide-treated rats (4,5).…”

Section: Effect Of 24-hr Water Deprivation In Conscious Wky and Shrsupporting

confidence: 80%

“…In addi tion, the present study shows that after 24 hr of water deprivation, the pressor response to i.c.v.-clonidine is abolished and a depressor response appears in both WKY and SHR. These results are consisitent with our previous reports that the clonidine-induced pressor re sponse was abolished by 48 hours of water deprivation (4) and by furosemide (5). Inasmuch as the inhibitory effect of furosemide was correlated with increased urine volume, we proposed that the inhibition is associated with loss of body fluid volume (5).…”

Section: Effect Of 24-hr Water Deprivation In Conscious Wky and Shrsupporting

confidence: 78%

“…of furosemide does not affect the pressor response to i.v. noradrenaline, a mixed a, and a 2-adrenoceptor ago nist (5). Thus, it is likely that electrolyte alterations caused by furosemide at the dose used in this study (5 mg/kg) have little effect on the binding activities of central or peripheral a2-adrenoceptors.…”

Section: Effect Of 24-hr Water Deprivation In Conscious Wky and Shrmentioning

confidence: 85%

“…Inasmuch as the inhibitory effect of furosemide was correlated with increased urine volume, we proposed that the inhibition is associated with loss of body fluid volume (5). The present finding that clonidine causes a marked depressor response in WKY and SHR pretreated with furosemide, and in those deprived of water, is also consistent with our pre vious reports of a depressor response to clonidine in water-deprived or furosemide-treated rats (4,5). Taken together, these results suggest that clonidine has not only an a 2-adrenoceptor and imidazoline-preferring receptor-mediated hypotensive effect but also an a2 adrenoceptor-mediated hypertensive effect.…”

Section: Effect Of 24-hr Water Deprivation In Conscious Wky and Shrmentioning

confidence: 99%

“…There fore, we have proposed that the pressor response is mediated by central a2-adrenoceptors (1,3). Recently, we have reported that a reduction in body fluid volume, which was caused by water deprivation for 48 hr or by the diuretic, furosemide, abolishes the clonidine-induced pressor response and potentiated the clonidine-induced depressor response; and this sug gested that the pressor response is influenced by body fluid volumes (4,5). We have proposed that the re sponse to clonidine has a centrally-mediated pressor component, which opposes the hypotensive effect, and that the pressor component of the response to clonidine is sensitive to the diuretic and to anesthesia.…”

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confidence: 99%

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Central .ALPHA.2-Adrenoceptor-Mediated Pressor Response to Clonidine in Conscious, Spontaneously Hypertensive Rats.

1992

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Pressor responses to intracerebroventricular (i.c.v.) injection of clonidine were investi gated in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Clonidine (1-10 ,ug, i.c.v.) caused a dose-dependent pressor response and decrease in heart rate in both SHR and WKY. In SHR, low doses (1, 2.5 ug) but not high doses (5, 10 jig) of i.c.v.-clonidine in duced a depressor response following the pressor response. Both pressor and depressor responses to i.c.v.-clonidine were significantly greater in SHR than in WKY. In both SHR and WKY , pressor re sponses to i.c.v.-clonidine were abolished by pentobarbital anesthesia, pretreatment with i .v. furosemide (5 mg/kg), 24-hr water deprivation and pretreatment with i.c.v.-yohimbine (100 ug) , but not by pretreatment with i.v.-yohimbine (100 ug) and i.c.v.-prazosin (10 ug). On the 1st day after surgery for arterial catheter implantation, SHR reduced their water intake, and i.c.v.-clonidine (5 ug) caused a slight pressor response, whereas the same dose of clonidine on the 7th day after surgery re sulted in a marked pressor response. These results suggest that clonidine caused a central a2 adrenoceptor-mediated pressor response, which is greater in SHR than in WKY and is sensitive to body fluid volume changes and anesthesia.

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Section: Effect Of 24-hr Water Deprivation In Conscious Wky and Shrsupporting

confidence: 80%

Section: Effect Of 24-hr Water Deprivation In Conscious Wky and Shrsupporting

confidence: 78%

Section: Effect Of 24-hr Water Deprivation In Conscious Wky and Shrmentioning

confidence: 85%

Section: Effect Of 24-hr Water Deprivation In Conscious Wky and Shrmentioning

confidence: 99%

mentioning

confidence: 99%

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Central .ALPHA.2-Adrenoceptor-Mediated Pressor Response to Clonidine in Conscious, Spontaneously Hypertensive Rats.

1992

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Pressor response to microinjection of clonidine into the hypothalamic paraventricular nucleus in conscious rats

et al. 1993

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Theoretical and practical applications of the intracerebroventricular route for CSF sampling and drug administration in CNS drug discovery research: A mini review

Kuo

Smith

2014

Journal of Neuroscience Methods

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Clinically, central nervous system (CNS) disorders account for more hospitalisations and prolonged care than almost all other diseases combined. In the preclinical setting, the intracerebroventricular (ICV) route for cerebrospinal fluid (CSF) sampling or dose administration in rodent models of human CNS disorders has potential to provide key insight on the pathobiology of these conditions. Low level neuroinflammation is present in >40% of patients with severe depression or schizophrenia and so comparative assessment of CSF composition between patients and rodent models of CNS disorders is potentially invaluable for hypothesis generation and for assessing rodent model validity. As molecules in the CSF have relatively low protein binding and are freely exchanged into the extracellular fluid of the brain parenchyma, supraspinal drug administration into the CSF can produce therapeutic drug concentrations in the brain. Direct administration of investigational agents into the CSF of the lateral ventricle of the brain enables intrinsic efficacy and adverse effect profiles to be evaluated without the confounding effects of drug metabolism, due to the low capacity of the CNS to metabolise exogenous compounds. It is our view that the ICV route for CSF sampling and for administration of novel drugs in development is under-utilised in preclinical research on CNS disorders. This is due to the high degree of technical skill and low margin for error associated with correct ICV guide cannula implantation in the rat. However, these technical challenges can be overcome by using standardised procedures and attention to detail during surgery and in the post-operative period.

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Furosemide inhibits the centrally‐mediated pressor response to clonidine in conscious, normotensive rats

Cited by 7 publications

References 14 publications

Central .ALPHA.2-Adrenoceptor-Mediated Pressor Response to Clonidine in Conscious, Spontaneously Hypertensive Rats.

Central .ALPHA.2-Adrenoceptor-Mediated Pressor Response to Clonidine in Conscious, Spontaneously Hypertensive Rats.

Pressor response to microinjection of clonidine into the hypothalamic paraventricular nucleus in conscious rats

Theoretical and practical applications of the intracerebroventricular route for CSF sampling and drug administration in CNS drug discovery research: A mini review

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