Zeman Michal, Petrák Juraj, Stebelová Katarína, Nagy György, Krizanova Olga, Herichová Iveta, Kvetnanský Richard
Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University Bratislava, Slovakia.
Ann N Y Acad Sci. 2008 Dec;1148:308-16. doi: 10.1196/annals.1410.069.
Hypertensive TGR(mRen2)27 (TGR) rats represent a strain with genetically upregulated renin-angiotensin-aldosterone system. Simultaneously with development of hypertension, a daily profile in blood pressure (BP) inverts and in mature TGR rats BP is higher during the lighttime (L) than the darktime (D). Physiological mechanisms of inverted BP rhythm generation are not understood. In our study we determined circadian profiles of plasma hormones related to BP control (aldosterone, corticosterone, melatonin, prolactin) in TGR and control Sprague-Dawley (SD) rats over 24 h and expression of genes encoding catecholamine synthesizing enzymes, tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT) in adrenals and stellate ganglia. Plasma levels of corticosterone and aldosterone were higher in TGR than SD rats but acrophases of their rhythms were not changed. Darktime peak of prolactin in TGR rats was decreased in comparison with SD animals and pineal melatonin levels started to rise earlier in TGR than in SD rats. In adrenals we found upregulated expression of TH, DBH, and PNMT mRNA at the beginning of the lighttime in TGR compared to SD rats. Expression of TH and DBH in stellate ganglia was not different in TGR rats in comparison with SD, but PNMT expression was higher during L compared to D in TGR rats. We hypothesize that upregulated adrenal medulla functioning in the morning and disturbed communication between circadian oscillators and mechanisms involved in BP control can explain the reversed BP profile in TGR rats.
高血压TGR(mRen2)27(TGR)大鼠是一种肾素-血管紧张素-醛固酮系统基因上调的品系。在高血压发展的同时,血压(BP)的日变化模式发生反转,在成熟的TGR大鼠中,白天(L)的血压高于夜间(D)。血压节律反转产生的生理机制尚不清楚。在我们的研究中,我们测定了TGR大鼠和对照Sprague-Dawley(SD)大鼠在24小时内与血压控制相关的血浆激素(醛固酮、皮质酮、褪黑素、催乳素)的昼夜变化情况,以及肾上腺和星状神经节中编码儿茶酚胺合成酶、酪氨酸羟化酶(TH)、多巴胺-β-羟化酶(DBH)和苯乙醇胺-N-甲基转移酶(PNMT)的基因表达。TGR大鼠的皮质酮和醛固酮血浆水平高于SD大鼠,但其节律的峰相位没有改变。与SD动物相比,TGR大鼠催乳素的夜间峰值降低,TGR大鼠松果体褪黑素水平比SD大鼠更早开始升高。与SD大鼠相比,我们发现TGR大鼠在白天开始时肾上腺中TH、DBH和PNMT mRNA的表达上调。与SD大鼠相比,TGR大鼠星状神经节中TH和DBH的表达没有差异,但TGR大鼠在白天L期间PNMT的表达高于夜间D。我们推测,TGR大鼠早晨肾上腺髓质功能上调以及昼夜振荡器与血压控制相关机制之间的通讯紊乱可以解释其血压模式的反转。