THYROTROPIN-RELEASING HORMONE (TRH) MAY MEDIATE SYMPATHETIC ACTION AND ARTERIAL BLOOD PRESSURE INCREASE IN OFFSPRING OF MATERNAL OBESITY. In: Hypertension. eLetters [Internet]. Dallas

LANDA, MARIA SILVINA; SCHUMAN, MARIANO LUIS; PERES DIAZ LUDMILA; GARCIA , SILVIA INES; PIROLA, CARLOS JOSE

HYPERTENSION

LIPPINCOTT WILLIAMS & WILKINS

Lugar: Philadelphia; Año: 2014 p. 1 - 2

0194-911X

THYROTROPIN-RELEASING HORMONE (TRH) MAY MEDIATE SYMPATHETIC  ACTION AND ARTERIAL BLOOD PRESSURE INCREASE IN OFFSPRING OF MATERNAL OBESITY. María S. Landa PhD 1, 2, Mariano L. Schuman PhD1,  Ludmila S. Peres Diaz1, Silvia I. García PhD 1and  Carlos J. Pirola PhD2. Laboratory of Molecular Cardiology 1 and Department of Molecular Genetics and Biology of Complex Diseases2.  Instituto de Investigaciones Médicas A. Lanari, Universidad de Buenos Aires IDIM-CONICET Buenos Aires, Argentina Recently, Prior et al (1) reported that offspring from high-fat diet (HFD)- exposed mothers at 4 month of age have increased visceral fat, elevated arterial blood pressure (ABP), heart rate and sympathetic nerve activity compared with those offspring from normal chow-fed mothers and shown a selective leptin-resistant phenotype. While the effect of HFD during pregnancy on metabolic syndrome component, in particular insulin resistance and visceral adipose tissue is known, we invite authors to consider that the diencephalic TRH (dTRH) system may be involved in the mechanism of preservation of sympathoexcitatory actions despite resistance to the anorexigenic and metabolic action of leptin. In this regards, we demonstrated that rats fed with HFD show an hyperactivity of the dTRH system  and  the knocking down of the prepro-dTRH gene by two different strategies normalizes ABP by decreasing the elevated concentrations of methanephrine and normethanephrine of obese animals (2). As Prior et al (1) suggests, maternal overnutrition appears to alter central appetite circuits. It has been reported that the activation of the melanocortin system pathway mediates, at least in part, the blood pressure effect of leptin by increasing RSNA (3). In fact, we have already reported that a melanocortin agonist acting on the MCR3 or 4 induced hypertension only in the presence of an intact TRH system. Hence, we postulate that the axis leptin-melanocortin-TRH might explain increases of ABP in different models of obesity-induced hypertension (4). We wish to report here that , SHR which presents dTRH overexpression and its consequent SNS hyperactivity,  shows increased levels of melanocortin system components (POMC : 1.053±0.250 vs 0.137±0.251 and MC4-R: 0.203±0.073 vs 0.044±0.84) and the antagonist MC4R (SHU-9119) was able to  reduce  dTRH  and significantly decrease BP. SHR rats were implanted with a guide cannula into the III ventricle (ICV) for SHU or vehicle infusion (V) as describe elsewhere. (5). Systolic, diastolic and media arterial blood pressure were measure by a tail-cuff method (CODA-4, Kent Scientific, Torrington, CT, USA) along with body weight, and food consumption in basal condition and 24 hours after icv injection of SHU (0.6nmol/5ul) and V(5ul) in awake chronically instrumented  rats. Animals were euthanized and the diencephalum was removed to measure TRH and POMC expression by PCR-real time. As expected, SHU induced an increase in food consumption and body weight. Accordingly to our hypothesis SHU decreased dTRH expression and ABP. GROUPS FOOD CONSUMPTION, g/day HEART RATE, beats/min SABP, mmHg TRH/HPRT BASAL POST-ICV BASAL POST-ICV BASAL POST ICV WKY-V 20.3±2.6 20.5±3.6 371,27±9.8 392,43±12.4 137.5±6.2 142.3±4.7 0.053±0.726 WKY-SHU 20.0±2.2 26.4±3.2 # 397,58±11.08 372,86±10.80 140.5±6.2 143.5±4.8 0.049±0.725 SHR-V 22.6±1.8 20.8±2.1 426,89± 9.76 446,25±21.10 219.1±5.1 227.1±3.8 1.403±0.592 SHR-SHU 21.2±2.1 28.8±2.9 # 438,11±19.9 350,40±10.90# 219.4±6.2 196.9±4.7 # 0.036±0.649 * * p<0.05 vs SHR-SHU, #: p<0.05 vs basal In summary, our results suggest that the leptin-melanocortin-dTRH axis may contribute to cardiovascular alterations found in the next generation of maternal overnutrition, which deserves further investigation. Sources of Funding These studies were supported by grants from the Agencia Nacional de Investigaciones Científicas y Técnicas (ANPCyT): PICT 2010-2581, 2010-0441 and CONICET  PIP Nº 11220090100636.  REFERENCES   (1)    Prior LJ, Davern PJ, Burke SL, Lim K, Armitage JA, Head GA. Exposure to a high-fat diet during development alters leptin and ghrelin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits. Hypertension. 2014;63(2):338-345.   (2)    Landa MS, Garcia SI, Schuman ML, Burgueno A, Alvarez AL, Saravia FE, Gemma C, Pirola CJ. Knocking down the diencephalic thyrotropin-releasing hormone precursor gene normalizes obesity-induced hypertension in the rat. Am J Physiol Endocrinol Metab. 2007;292(5):E1388-E1394.   (3)    da Silva AA, do Carmo JM, Hall JE. Role of leptin and central nervous system melanocortins in obesity hypertension. Curr Opin Nephrol Hypertens. 2013;22(2):135-140.   (4)    Landa MS, Garcia SI, Schuman ML, Alvarez AL, Finkielman S, Pirola CJ. Thyrotropin-Releasing Hormone Precursor Gene Knocking Down Impedes Melanocortin-Induced Hypertension in Rats. Hypertension. 2008;52(2):e8.   (5)    Garcia SI, Landa MS, Porto PI, Alvarez AL, Schuman M, Finkielman S, Pirola CJ. Thyrotropin-releasing hormone decreases leptin and mediates the leptin-induced pressor effect. Hypertension. 2002;39(2 Pt 2):491-495.