Pre-weaning carvedilol treatment in spontaneously hypertensive rats

Boesen, Erika I.; Lambert, Gavin; Anderson, Warwick P.; Kett, Michelle M

doi:10.1016/j.ejphar.2003.12.012

Cited by 3 publications

(2 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, in pre-hypertensive and hypertensive SHR, there is increased functional b 2 -adrenoceptor response [44,45]. Furthermore, pre-weaning treatment of SHR with the b-blocker carvedilol reduced blood pressure during treatment and attenuated the subsequent development of hypertension [46]. Therefore, although adrenaline plasma levels remain similar to the normotensive strain during the onset of hypertension, activation of presynaptic b 2 -adrenoceptors could cause enhanced noradrenaline release, a factor associated with the onset of hypertension.…”

Section: Discussionmentioning

confidence: 99%

α2-Adrenoceptor-Mediated Inhibition of Catecholamine Release from the Adrenal Medulla of Spontaneously Hypertensive Rats is Preserved in the Early Stages of Hypertension

Moura

Pinto

Caló

et al. 2011

Basic &Amp; Clinical Pharmacology &Amp; Toxicology

View full text Add to dashboard Cite

In this study, we evaluated the effect of a 2 -adrenoceptor activation on catecholamine release from the adrenal medulla of pre-hypertensive (6-week-old) and hypertensive (16-week-old) spontaneously hypertensive rats (SHR) and of agematched normotensive control Wistar Kyoto (WKY) rats. Catecholamine overflow from isolated adrenal medullae was evoked by the nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) in the absence and presence of the a 2 -adrenoceptor agonist medetomidine (MED). The spontaneous outflow of adrenaline was similar between age-matched SHR and WKY rats. However, the spontaneous outflow of noradrenaline was significantly lower in SHR compared with agematched WKY rats. DMPP (0.1-3 mM) increased the outflow of noradrenaline and adrenaline in a concentration-dependent manner. The E max values for adrenaline overflow were similar between strains, but the E max values for noradrenaline overflow were significantly lower in SHR. The EC 50 values for noradrenaline and adrenaline overflow were significantly higher in SHR compared with age-matched WKY rats. MED (0.1-300 nM) reduced the DMPP-evoked overflow (DMPP 500 lM) of noradrenaline and adrenaline in a concentration-dependent manner and was capable of totally inhibiting this effect. The inhibitory action of MED was similar between age-matched SHR and WKY rats. In the adrenals, the a 2A -and a 2B -adrenoceptor subtypes had the highest mRNA expression levels; the a 2C -adrenoceptor subtype had the lowest mRNA expression levels. The mRNA levels for the three subtypes were similar between strains. In conclusion, in SHR during the development of hypertension, adrenal a 2 -adrenoceptor inhibitory function is conserved, accompanied by reduced noradrenaline release and unchanged adrenaline release. a 2 -Adrenoceptors are important target molecules for endogenous catecholamines and exogenous pharmacological agents. a 2 -Adrenoceptors consist of three genetically distinct subtypes, a 2A , a 2B and a 2C [1]. Presynaptic a 2 -adrenoceptors play a critical role in regulating noradrenaline release from sympathetic nerve terminals by a negative feedback mechanism [2,3]. Moreover, a 2 -adrenoceptors are solely responsible for autocrine feedback inhibition of noradrenaline and adrenaline secretion from the adrenal medulla [4][5][6][7].Increased activity of the sympathetic nervous system (SNS) accompanied by increased noradrenaline spillover has been implicated in the pathogenesis of essential hypertension in humans [8][9][10] and in an animal model of this disorder, the spontaneous hypertensive rat (SHR) [11,12]. Impairment of presynaptic a 2 -adrenoceptors by a reduced expression of the a 2A -adrenoceptor subtype has been associated with the increased noradrenaline release that is associated with the hypertensive phenotype in SHR [13,14].The adrenal medulla in combination with the SNS also plays a role in the epigenesis of hypertension in SHR. Hypertension and left ventricular hypertrophy were absent only in sympathectomized SHR tha...

show abstract

Section: Discussionmentioning

confidence: 99%

α2-Adrenoceptor-Mediated Inhibition of Catecholamine Release from the Adrenal Medulla of Spontaneously Hypertensive Rats is Preserved in the Early Stages of Hypertension

Moura

Pinto

Caló

et al. 2011

Basic &Amp; Clinical Pharmacology &Amp; Toxicology

View full text Add to dashboard Cite

show abstract

“…Given that in this study, we began treatment with clonidine in young normotensive spontaneously hypertensive rats, rather than hypertensive rats, the question of whether or not this treatment abolishes or attenuates the development of hypertension in spontaneously hypertensive rats remains open. In a previous study, pre‐weaning treatment with the α 1 /β‐adrenoceptor antagonist carvedilol attenuated, but did not prevent the development of hypertension in spontaneously hypertensive rats [46]. It would also be interesting to see if a similar treatment targeting of α 2 ‐adrenoceptors would be able to abolish the development of hypertension in spontaneously hypertensive rats.…”

Section: Discussionmentioning

confidence: 99%

Effect of Clonidine on Tyrosine Hydroxylase Activity in the Adrenal Medulla and Brain of Spontaneously Hypertensive Rats

Moura

Afonso

Serrão

et al. 2009

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Abstract:In the present study, we evaluated the effect of the α 2 -adrenoceptor agonist clonidine on tyrosine hydroxylase activity in adrenal medulla and brain of spontaneously hypertensive rats and Wistar Kyoto rats. Six-week-old animals were treated with clonidine (100 μ g/kg body weight, daily, i.p.) for 4 weeks. Treatment with clonidine significantly reduced mean arterial blood pressure in spontaneously hypertensive rats to values similar to normotensive Wistar Kyoto rats. In the adrenal medulla of spontaneously hypertensive rats, clonidine treatment produced a significant increase in tyrosine hydroxylase activity with higher V max values and no changes in K M values. This effect was accompanied by a significant increase in tyrosine hydroxylase protein expression and of noradrenaline and adrenaline levels. In the brain of spontaneously hypertensive rats, treatment with clonidine produced a significant decrease in tyrosine hydroxylase activity with lower V max values and no changes in K M values accompanied by a significant decrease in tyrosine hydroxylase protein expression and of dopamine and noradrenaline levels. In Wistar Kyoto rats, clonidine treatment had no effect on tyrosine hydroxylase activity and protein expression or catecholamine levels in adrenal medulla or brain. Clonidine treatment significantly reduced noradrenaline and adrenaline plasma levels in spontaneously hypertensive rats and Wistar Kyoto rats. In conclusion, treatment with the α 2 -adrenoceptor agonist clonidine prevented the increase in mean arterial blood pressure in young spontaneously hypertensive rats. This effect was accompanied by opposite effects on tyrosine hydroxylase activity in spontaneously hypertensive rat adrenal medulla and brain: an increase in adrenal medulla and a decrease in brain, bringing sympathetic function to a similar profile found in normotensive Wistar Kyoto rats.The endogenous catecholamines noradrenaline and adrenaline mediate sympathetic regulation of blood pressure [1]. These effectors of the sympathetic nervous system are synthesized within sympathetic neurons and chromaffin cells of the adrenal medulla by a well-defined series of reactions that start with the conversion of tyrosine to 3,4-dihydroxyphenylalanine mediated by tyrosine hydroxylase, the initial and rate-limiting enzyme of the pathway [2]. Noradrenaline is the principal neurotransmitter of sympathetic neurons, whereas adrenaline is secreted from the chromaffin cells of the adrenal medulla into the circulation. Whereas the actions of noradrenaline are mostly restricted to the sites of release from sympathetic nerves, adrenaline acts as a neurohormone to activate cardiovascular and metabolic responses via the blood stream.Increased sympathetic nervous system activity with higher tyrosine hydroxylase activity and catecholamine levels are common features of hypertension in human beings and in the spontaneously hypertensive rat [3,4], an animal model used to investigate the mechanisms of essential hypertension [5]. It is noteworthy that in spont...

show abstract

Inhibition of Ethanol-Induced Gastric Mucosal Damage by Carvedilol in Male Wistar Albino Rats: Possible Biochemical Changes

Al-Rejaie¹

2009

International J. of Pharmacology

View full text Add to dashboard Cite

Pre-weaning carvedilol treatment in spontaneously hypertensive rats

Cited by 3 publications

References 20 publications

α2-Adrenoceptor-Mediated Inhibition of Catecholamine Release from the Adrenal Medulla of Spontaneously Hypertensive Rats is Preserved in the Early Stages of Hypertension

α2-Adrenoceptor-Mediated Inhibition of Catecholamine Release from the Adrenal Medulla of Spontaneously Hypertensive Rats is Preserved in the Early Stages of Hypertension

Effect of Clonidine on Tyrosine Hydroxylase Activity in the Adrenal Medulla and Brain of Spontaneously Hypertensive Rats

Inhibition of Ethanol-Induced Gastric Mucosal Damage by Carvedilol in Male Wistar Albino Rats: Possible Biochemical Changes

Contact Info

Product

Resources

About