The partlclpatlon of substance Pm the pathogenesls of five models of expenmental hypertension, le, DOCA-salt, subtotal nephrectomy, one-kidney-one chp renovascular, two-kldney-one clip renovascular, and spontaneous hypertension, was evaluated via an acute infusion of a newly synthesized potent, specific nonpeptlde antagonist of substance P at the NK-1 receptor, the agent CP 96,345 In conscious unrestrained rats, CP 96,345 induced significant and sustained increases m mean arterial pressure of DOCA-salt, subtotal nephrectomy, and onekidney-one clip renovascular hypertensive rats but only small and nonslgmficant changes m blood pressure of two-hdney-one chp renovascular and spontaneously hypertensive rats CP 96,345 had no effect on the blood pressure of sham-treated controls and Wlstar-Kyoto rats This NK-1 receptor antagomst did not sIgnifscantly affect the heart rate of any expenmental model studied The data suggest that endogenous substance P may act as a partial counterregulatory mechanism against vasoconstrlctlon m models of salt-dependent hypertension (Hypertension. 1997;29[part 21: 506-509.) Key Words l experlmental hypertension l sodlumdependent hypertension l substance P l receptors NK-I l tachyknuns S ubstance P, a member of the family of tachykmms,' 1s involved m numerous physlologlcal actlvmes, such as neurotransmlssion-neuromodulatlon,*,3 stlmulatlon of salivary secretIon, smooth muscle contraction,5 and vasodilatlon.6.7The vasochlatory action of substance P 1s endothelmm dependentg9 and is mediated by the neurokmm NK-1 receptors located on the endothehal cells. Besides its vasodllatory properties, m some vascular beds substance P also exerts a contracting action on the vascular smooth muscle lo-12 These vasoactlve properties of substance P enable this peptide to participate m the regulation of blood flow of various organs 5.6The participation of endogenous substance P in hypertension has been evaluated by a few mvestlgators, mainly by measurement of the plasma levels of this peptide,'? 14 whereas the pharmacological effects have been explored by administration of synthetic substance P or related analogues 15.16 Reduced plasma levels of this peptlde have been described m both stroke-prone spontaneously hypertensive rats 13 and m human essential hypertennon, 14 suggestmg that elevated blood pressure m these SubJects could be related, at least m part, to the lack of adequate counterregulatory action exerted by this endogenous vasodllator.Recently, a potent, specific, nonpeptlde antagonist of the NK-1 receptor, devoid of agomstlc actions was syn- In previous studies from our laboratories, we were able to demonstrate that an acute mfuslon of this compound increases blood pressure of DOCA-salt hypertensive rats m the early stages (6 weeks) of the hypertensive state However, when we Infused the same agent m rats at later phases of DOCA-salt hypertension (12 weeks), no wgmficant increases m blood pressure were observed 1~0 These observations suggest that partlclpatlon of substance P m the pathoge...

For better understanding the role of each element involved in the physiopathology of obesity and insulin resistance, researchers can use experimental models, which may in controlled manner evaluate the participation of each element on the obesity and insulin resistance and provide information for better understanding the physiopathology and treatment of obesity and insulin resistance. Experimental obesity and insulin resistance can be due to a deficient response to leptin, secondary to hypoleptinemia and/or mutations on leptin receptor, by modifications on insulin receptor, deletion or diminished insulin signal transduction, enhancement of the effects of orexigen peptides and/or diminution of anorexigen peptides actions on hypothalamus, as well as secondary to arterial hypertension, as in the spontaneously hypertension. Obesity and insulin resistance can also be induced by glucocorticoid excess, frutose enriched and cafeteria diet and due to hypothalamus lesions induced by neonatal administration of monossodium glutamate.

Escitalopram decreases HR, but not BP, in individuals with hypertension and depression. Abbreviation: SH: systemic hypertension; BP: blood pressure; DSM: Diagnostic and Statistical Manual of Mental Disorders; SRQ 20: Self-Report Questionnaire; SCID: Structured Clinical Interview for DSM-IV; HR: heart rate; SNS: Sympathetic nervous system; HPA: hypothalamus-pituitary-adrenal axis; RAA: renin, angiotensin, aldosterone system; NE: norepinephrine; CSF: cerebrospinal fluid; HAM-D: Hamilton Depression Rating Scale; CRF: corticotropin releasing factor; ACTH: adrenocorticotropic hormone; BMI: Body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; t: time.

RESUMOO objetivo do estudo foi avaliar o efeito da obesidade induzida pela administração neonatal de glutamato monossódico (MSG) sobre o peso corporal, a pressão arterial de cauda, a hemodinâmica sistêmica e a função ventricular esquerda de ratos Wistar. Dois grupos de ratos Wistar foram preparados: a)18 animais foram tornados obesos por meio da administração de 2 mg/kg/SC de MSG durante os 11 primeiros dias do período neonatal e b)16 animais controles (que receberam o veículo do MSG pelo mesmo período). Animais adultos foram acompanhados dos três aos seis meses de vida e tiveram pressão arterial e peso corporal medidos duas vezes por semana. Ao final desse período, em parte dos animais dos dois grupos, avaliou-se a função ventricular por intermédio da preparação do coração isolado de Langerdorff, e os animais restantes foram usados para o estudo da hemodinâmica sistêmica por meio de um método de termodiluição. Resultados: Nos animais MSG houve aumento da gordura epididimal relativa (WST = 2,076 ± 0,622; MSG = 2,731 ± 0,722 g/100 g), aumento significante da freqüência cardíaca (WST = 235,0 ± 35,1; MSG = 312,0 ± 90,8 bpm), da resistência periférica total (WST = 0,312 ± 0,100; MSG = 0,535 ± 0,195 mmHg.ml The aim of this study was to evaluate the effects of obesity induced by neonatal Monosodium Glutamate (MSG) administration upon body weight, tail blood pressure, systemic hemodynamics and left ventricular function of Wistar rats. Two groups of Wistar rats were prepared: a) 18 animals made obese through the administration of 2mg/Kg/SC of MSG during the first 11 days of the neonatal period and b)16 control animals (vehicle treated for the same period). Adults animals were followed from the 3rd up the 6th month of life with blood pressure and body weight being measured twice a week. At the end of this period, in part of animals from both groups, we evaluated the left ventricular function through the Langendorff isolated heart preparation whereas the remainders were used to evaluate the systemic hemodynamics through a termodilution method. Results: MSG animals showed significant increases in heart rate (WST = 235,0 ± 35,1; MSG = 312,0 ± 90,8 bpm), total peripheral resistance (WST = 0,312 ± 0,100; MSG = 0,535 ± 0,195 mmHg.ml -1 .

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