Resistance to salt-induced hypertension in catechol-O-methyltransferase-gene-disrupted mice
作者:
Teemu Helkamaa,
Pekka Männistö,
Pekka Rauhala,
Zhong Cheng,
Piet Finckenberg,
Marko Huotari,
Joseph Gogos,
Maria Karayiorgou,
Eero Mervaala,
期刊:
Journal of Hypertension
(OVID Available online 2003)
卷期:
Volume 21,
issue 12
页码: 2365-2374
ISSN:0263-6352
年代: 2003
出版商: OVID
关键词: catechol-O-methyltransferase;L-3;4-dihydroxyphenylalanine (l-DOPA);dopamine;noradrenaline;blood pressure;sodium;kidney
数据来源: OVID
摘要:
BackgroundPrevious studies have indicated that catechol-O-methyltransferase (COMT) can modulate renal dopaminergic tone.ObjectiveTo test the hypothesis that COMT blockade protects from salt-induced hypertension.MethodsCOMTgene-disrupted (−/−) mice and wild-type controls received a high-sodium diet (NaCl 6%) for 3 weeks. Blood pressure and heart rate were recorded by radiotelemetry. Tissue and urine samples were assessed by light microscopy and high-performance liquid chromatography. The effects of nitecapone treatment were also examined. Systolic blood pressure and heart rate during normal sodium diet were similar inCOMT(−/−) and wild-type mice. The high-sodium diet increased night-time systolic and diastolic blood pressures in wild-type mice, whereas blood pressure inCOMT(−/−) mice remained unaltered. In wild-type mice, the sodium-induced increase in blood pressure was completely normalized by treatment with the COMT inhibitor, nitecapone. At baseline, 24-h urinary excretion of levodopa (l-DOPA), dopamine and noradrenaline was increased by 145, 85 and 74%, respectively, inCOMT(−/−) mice compared with wild-type controls. InCOMT(−/−) and wild-type mice, a high-sodium diet increased urinary l-DOPA excretion by 405 and 660% (reflected as 102 and 212% increases in dopamine excretion), respectively. The absolute amounts of urinary l-DOPA and dopamine remained 60 and 20% greater inCOMT(−/−) mice. The high-sodium diet did not influence renal cortical COMT activity.ConclusionOur findings suggest that COMT deficiency in mice increases the availability of l-DOPA, leading to enhanced dopaminergic tone, which may be associated with resistance to salt-induced hypertension. The findings of the present study also underline the importance of COMT in the regulation of blood pressure, sodium excretion and renal dopaminergic tone.
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