TY - JOUR
T1 - Pre-weaning carvedilol treatment in spontaneously hypertensive rats
AU - Boesen, Erika I.
AU - Lambert, Gavin W.
AU - Anderson, Warwick P.
AU - Kett, Michelle M.
N1 - Funding Information:
This work was supported by the National Health and Medical Research Council of Australia (project grant 124404) and GlaxoSmithKline. Erika Boesen held an Australian Postgraduate Award and a Monash University Post-Graduate Excellence Award. The authors wish to thank Katrina Worthy, Angela Gibson (plasma creatinine measurements) and Dr. Amany Shweta (immunohistochemistry) for their assistance in conducting this study.
PY - 2004/2/20
Y1 - 2004/2/20
N2 - Hypertension in spontaneously hypertensive rats (SHR) has been permanently abolished by aggressive treatment regimens targeted against the sympathetic nervous system and adrenal medulla, initiated during the pre-weaning period (guanethidine and nerve growth factor antiserum combined with either adrenal demedullation or prazosin treatment). To investigate the components of the sympatho-adrenal system involved, we treated pre-weaning SHR with the combined α1- and β-adrenoceptor antagonist carvedilol (60 mg/kg/ day s.c.; postnatal days 1-21). Carvedilol treatment significantly blocked adrenoceptors during the treatment period, delayed development (eye opening), reduced growth, and reduced arterial pressure and heart rate. However, there was only modest attenuation of the subsequent development of hypertension at 10 weeks of age (mean arterial pressure 129.5±1.8 versus 136.1±1.6 mm Hg in vehicle-treated littermates; P<0.05). Thus pre-weaning carvedilol treatment slightly but significantly attenuated the development of SHR hypertension at 10 weeks, suggesting that the profound antihypertensive effects of pre-weaning sympatho-adrenal ablation are attributable to factors other than α1- and β-adrenoceptor-mediated effects of catecholamines during this period.
AB - Hypertension in spontaneously hypertensive rats (SHR) has been permanently abolished by aggressive treatment regimens targeted against the sympathetic nervous system and adrenal medulla, initiated during the pre-weaning period (guanethidine and nerve growth factor antiserum combined with either adrenal demedullation or prazosin treatment). To investigate the components of the sympatho-adrenal system involved, we treated pre-weaning SHR with the combined α1- and β-adrenoceptor antagonist carvedilol (60 mg/kg/ day s.c.; postnatal days 1-21). Carvedilol treatment significantly blocked adrenoceptors during the treatment period, delayed development (eye opening), reduced growth, and reduced arterial pressure and heart rate. However, there was only modest attenuation of the subsequent development of hypertension at 10 weeks of age (mean arterial pressure 129.5±1.8 versus 136.1±1.6 mm Hg in vehicle-treated littermates; P<0.05). Thus pre-weaning carvedilol treatment slightly but significantly attenuated the development of SHR hypertension at 10 weeks, suggesting that the profound antihypertensive effects of pre-weaning sympatho-adrenal ablation are attributable to factors other than α1- and β-adrenoceptor-mediated effects of catecholamines during this period.
KW - Andrenoceptor antagonist
KW - Spontaneously hypertensive rat (SHR)
KW - Sympathetic nervous system
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U2 - 10.1016/j.ejphar.2003.12.012
DO - 10.1016/j.ejphar.2003.12.012
M3 - Article
C2 - 14975707
AN - SCOPUS:1242306190
SN - 0014-2999
VL - 486
SP - 183
EP - 188
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -