Morfo-anatomía foliar de Araujia odorata (Apocynaceae-Asclepiadoideae) en un gradiente altitudinal: histoquímica de laticíferos / Foliar morpho-anatomy of Araujia odorata (Apocynaceae-Asclepiadoideae) in an altitudinal gradient: histochemistry of laticifers

Araujia odorata is a sub-shrub native from Argentina, Brazil, Paraguay and Uruguay, whose latex, roots and leaves are used in traditional medicine. The objective of this work is to study the foliar morpho-anatomy of six populations in an altitudinal gradient (359-2155 m.a.s.l.) of Northwestern Argentine and to determine the nature of the compounds present in the laticiferous of the stems and fruits using conventional techniques for plant anatomy. The populations under study did not show significant morpho-anatomical differences. They presented simple leaves, pinnated brochydodromous venation, amphiestomatic isolateral lamina, brachy, anomo and amphicyclocytic stomata, eglandular trichomes, midvein with bicolateral vascular bundle and non-articulated laticifers continuous in the petiole, stem and fruits. Differences in the quantified foliar parameters are observed, however, only the density of trichomes, stomata and the thickness of the cuticle are positively correlated with the altitudinal gradient, indicating phenotypic plasticity. Histochemical analysis of laticifers and other stem idioblasts of A. odoratawas performed for the first time.

Araujia odorata, es un subarbusto nativo de Argentina, Brasil, Paraguay y Uruguay, cuyo látex, raíces y hojas son utilizados en medicina popular. Se plantea como objetivo realizar un estudio morfo-anatómico foliar de seis poblaciones del Noroeste Argentino en un gradiente altitudinal (359-2155 m.s.n.m) y determinar la naturaleza de los compuestos presentes en laticíferos de tallos y frutos mediante técnicas convencionales de anatomía vegetal. Las poblaciones estudiadas no evidenciaron diferencias morfo-anatómicas significativas. Presentan hojas simples, venación pinnada broquidódroma, lámina isolateral anfiestomática, estomas braqui, anomo y anficiclocíticos, tricomas eglandulares, nervio medio con haz bicolateral y laticíferos no-articulados continuos en pecíolo, tallo y frutos. Se observan diferencias en los parámetros foliares cuantificados, sin embargo, solo la de densidad de tricomas, estomas y el espesor de cutícula se correlacionan positivamente con el gradiente altitudinal indicando plasticidad fenotípica. Se realiza por primera vez un análisis histoquímico de los laticíferos y otros idioblastos del tallo A. odorata.

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

Estudo da superposição de mecanismos fisiopatológicos como modelo de hipertensão arterial com repercussões cardíacas graves / Study of overlap of pathophysiologicalmechanisms as a model of hypertensionwith severe cardiac effects

Fundamento: Acredita-se que o rato espontaneamente hipertenso (SHR) mimetize a hipertensão arterial (HA) essencial em humanos. Lesões em órgãos-alvo nesses animais não são devidas unicamente ao aumento da pressão arterial. Outros mecanismos fisiopatológicos superajuntados talvez representem melhor o complexo dano cardiovascular observado também em humanos. Objetivo: avaliar, comparativamente, as alterações cardíacas em ratos SHR nos quais mecanismos outros de HA (renovascular, hipervolemia, disfunção endotelial) sejam superpostos. Materiais e Métodos: cinco grupos foram estudados: Controle (C,n=11); SHR (n=11); SHR + L-NAME (SHR + L-NAME, n=11); SHR com estenose cirúrgica de artéria renal (SHR + 2R-1C, n=11); SHR+ deoxicorticosterona e cloreto de sódio 0,9% (SHR+DOCA-SALT, n = 11). Foram avaliados pressão arterial caudal (PAC), hipertrofia do ventrículo esquerdo (VE) e alterações histológicas miocárdicas. Resultados: Após oito semanas, os grupos SHR + L-NAME, SHR + 2R-1C e SHR + DOCA-SALT mantiveram PAC semelhante e mais elevada que os animais SHR (159,9 ± 8,3; 162,7± 16,7 e 166,3 ± 6,7 versus 138±7,8, respectivamente), bem como a espessura relativa da parede do VE (SHR + L-NAME = 0,64 ± 0,06; SHR+DOCA-SALT=0,63 ± 0,07 versus SHR=0,57±0,03) (p < 0,05). Amassa relativa do VE dogrupo SHR+ L-NAME (4,2±1,15) foi maior que nos demais grupos (SHR=2,8±0,5; SHR + 2R-1C=3,2±0,5; SHR + DOCA-SALT = 3,1 ± 0,2) (p <0,05). O desarranjo de fibras, fibrose intersticial, espessura médio-intimal aumentada foram mais frequentes nos ratos SHR + L-NAME. Conclusão: O modelo SHR + L-NAME mostrou repercussões cardíacas mais evidentes que os demais modelos de HA, fato não explicado apenas pelos níveis de PA elevados. Tal modelo pode ser utilizado em estudos futuros como representativo de maior comprometimento cardíaco na HA grave ou em estados avançados da doença.

Background: Spontaneously hypertensive rats (SHR) are believed to mimic arterial hypertension (HA) essential in humans. The injuries on targeted organs on these animals are not due only to increased blood pressure. Other pathophysiological mechanisms may represent better the superimposed complex cardiovascular damage observed on humans as well. Objective: comparatively evaluate the cardiac abnormalities in SHR in which other mechanisms of hypertension (renovascular, fluid overload and endothelial dysfunction) are superimposed. Materials and Methods: 5 groups were studied: Control (C, n=11); SHR (n = 11); SHR + L-NAME (SHR + L-NAME, n= 11), SHR with surgical stenosis of renal artery (SHR+ 2K-1C, n = 11), SHR + deoxycorticosterone and sodium chloride 0.9% (SHR + DOCA-SALT, n = 11). The blood pressure flow (PAC), left ventricular hypertrophy (VE) (echocardiography) and myocardial histological changes were evaluated. Results:After 8 weeks, the SHR + L-NAME, SHR + 2K-1C and SHR + DOCA-SALT groups maintained similar and higher PAC than SHR (159.9 ± 8.3, 162.7 ± 16.7 and 166.3 ± 6.7 versus 138± 7.8, respectively) as well as the relative thickness of the VE wall (SHR + L-NAME = 0.64 ± 0.06, SHR + DOCA-SALT= 0, 63 ± 0.07 versus SHR = 0.57 ±0.03;) (p < 0.05). The relative LV mass (MRVE, mg/g) of the group SHR + L-NAME (4.2 ± 1.15) was higher than in other groups (SHR = 2.8 ± 0.5, SHR + 2K-1C = 3.2±0.5, SHR + DOCA-SALT = 3.1 ± 0.2) (p < 0.05). Fiber disarray, interstitial fibrosis and the increased of intima-media thickness were more frequent in SHR + L-NAME. Conclusion: SHR + L-NAME showed cardiac effects more evident than the other models of hypertension, which was not explained only by high levels of PA. This model can be used in future studies as representative of greater cardiac involvement in hypertension or severe stages of the disease.

Effect of Central Losartan on DOCA-Salt Hypertension Rats

BACKGROUND: The purpose of this study was to investigate whether brain AT1 receptor stimulation contributes as a hypertensive mechanism to deoxycorticosterone acetate (DOCA)-salt hypertension. METHODS: 1) Acute injection:Losartan (1 mg/4 uL) or artificial cerebrospinal fluid (aCSF) was injected into the lateral cerebral ventricle (icv) of conscious control uninephrectomized Wistar rats or rats with DOCA-salt at 2 or 4 weeks, and mean arterial pressure (MAP) and heart rates (HR) were recorded. 2) Chronic injection:Using osmotic minipump, losartan (1 mg/kg/d) or aCSF was injected to a sham group or three DOCA-salt rat groups [icv-aCSF, icv-losartan, sc-losartan (subcutaneous) groups] for 4 weeks, after which the MAP and HR were recorded in addition to the weights of the left (LV) and right ventricles (RV) and kidneys. RESULTS: 1) Acute injection: In rats treated with DOCA-salt, resting MAP significantly increased compared to the control group [144+/-6 mmHg (2 weeks), 170+/-5 mmHg (4 weeks) vs 115-120 mmHg (controls)]. MAP decreased significantly (2 weeks, 4 weeks) at 4, 8, 24 hours after icv injection of losartan to the level of the control group. 2) Chronic injection: The general trend showed that MAP decreased more in the icv-losartan group than in the icv-aCSF group (127+/-15.2 mmHg vs 141.1+/-5.5 mmHg, p=0.0578). In all DOCA-salt groups, no differences in RV weight were found. In the icv-aCSF and sclosartan groups, the kidney weight increased compared to the control group, but there was no difference in LV and kidney weight between the icv-losartan group and the control group. CONCLUSION: Normalization of MAP after acute or chronic icv administration of the AT1 receptor antagonist suggests that the stimulation of the brain AT1 receptor plays a significant role in the development and maintenance of hypertension in the DOCA-salt hypertensive rat model. Losartan icv injection appeared to have a protective effect on the heart and kidney.

Time-Related Alterations of Endogenous Ouabain in DOCA-Salt Hypertensive Rats

BACKGROUND AND OBJECTIVES: Controversy exists regarding the role of endogenous ouabain in the pathogenesis of DOCA-salt induced hypertension. The purpose of this study was to investigate the role of endogenous ouabain in the development of hypertension in DOCA-salt rats. MATERIALS AND METHODS: The mean blood pressure and heart rate were recorded in 1, 2 and 4 week old control and DOCA-salt treated rats. The endogenous levels of ouabain in the plasma, hypothalamus, pituitary and adrenal glands of the 1, 2 and 4 week old control and DOCA-salt treated rats were also measured using a radioimmunoassay. RESULTS: The mean blood pressures in the 2 and 4 week old DOCA-salt treated rats were significantly higher than those of the controls. There was no significant change in the heart rate between the DOCA-salt treated and control groups. In the 4 week old DOCA-salt treated rats, the endogenous level of ouabain in the adrenal glands was higher than that in the control rats, but this was only weakly significant. The endogenous level of ouabain in the hypothalamus was significantly higher in the 1 week old DOCA-salt treated rats than in the control, but this significance disappeared in the 2 and 4 week old DOCA-salt treated rats. CONCLUSION: These results suggest that the endogenous level of ouabain contributes to the development and maintenance of high blood pressure in DOCA-salt rats. Further studies will be required to elucidate the relationship between the endogenous level of ouabain and DOCA-salt hypertension.

Aprovechamiento de Morrenia odorata (Hook & Arn.) Lindl. (Asclepiadeceae) «TASI¼ en medicina tradicional como una alternativa en la alimentación humana / Use of Morrenia odorata (Hook & Arn.) Lindl. (Asclepiadeceae) «TASI¼ in traditional medicine as an alternative in human nutrition

Es importante la revalorización de especies naturales usadas como fármacos respecto de los productos de síntesis en regiones donde la tradición milenaria de los aborígenes ha convertido a los vegetales en recursos muy apreciados para una medicina natural utilizada, principalmente, por aquellos que no pueden acceder a las tratamientos de la medicina clásica. La creciente conciencia sobre la necesidad de preservar el patrimonio vegetal natural frente a la pérdida de especies por la acción depredadora del hombre, ha reavivado el interés en el conocimiento y estudio de las especies nativas. El objetivo del trabajo fue determinar en Morrenia odorata (Hook & Am.) Lindl., la presencia de sustancias farmacológicamente activas o que pudieran resultar tóxicas para el consumo humano. También se investigó la composición físico-química de los frutos mediante la aplicación de reacciones específicas. Los resultados de los ensayos de toxicidad en M. odorata muestran que la misma es apta para el consumo humano con fines terapéuticos. en medicina tradicional, preparada como decocción e infusión de raíz, hojas y frutos. Del análisis del contenido nutricional de los frutos, se deduce que M. odorata contiene cantidades más elevadas de los componentes mayoritarios y un mayor aporte energético respecto a otros frutos convencionales. Estos resultados permitirán la difusión del consumo de los frutos de esta especie como una alternativa en la alimentación humana.

Altered vascular calcium regulation in hypertension

The present study was aimed at investigating whether the vascular calcium regulation is altered in hypertension. Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were made in rats, and their thoracic aortae were taken 4 weeks later. The isometric contractile response and calcium uptake of the endothelium-denuded aortic preparations were determined. Caffeine (0.1-35 mmol/L) induced a greater contraction in 2K1C and DOCA-salt hypertension than in normotensive control. When the vascular calcium store was functionally-depleted by a repeated exposure to caffeine, it took longer to reload the store and to resume the initial contraction force in response to caffeine in both 2K1C and DOCA-salt hypertension. The vascular 45Ca uptake following the functional depletion of the cellular store was also greater in both models of hypertension than in control. Ryanodine, calcium channel activator of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced vascular contraction, which was not affected by either 2K1C or DOCA-salt hypertension. Nifedipine, an L-type Ca2+ channel blocker, attenuated the restoration of caffeine-induced contraction, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Nifedipine also diminished the vascular 45Ca uptake, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Ouabain, a Na+, K+/-ATPase inhibitor, increased the caffeine-induced contraction by a similar magnitude in control and 2K1C hypertension, which was, however, markedly attenuated in DOCA-salt hypertension. Ouabain enhanced the vascular 45Ca uptake, the degree of which was not affected by 2K1C hypertension, but was markedly attenuated in DOCA-salt hypertension compared with that in control. Cyclopiazonic acid, a selective inhibitor of Ca2+/-ATPase of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced contraction, which was not affected by 2K1C hypertension, but was more marked in DOCA-salt hypertension. These results suggest that the increased vascular calcium storage may be attributed to an enhanced calcium influx in 2K1C hypertension, and to an impaired Na+/-K+ pump activity of the, cell membrane and subsequently increased calcium pump activity of the cellular store in DOCA-salt hypertension.

Establishment of the DOCA-Salt hypertensive rat model / 中国药理学通报

Aim To establish a reliable and practical rat model with hypertension induced by DOCA-Salt.Methods One week after nephrectomy,the rats were subcutaneously injected with DOCA (30 mg?kg-1) once a week and fed with a chaw with 10 g?L-1NaCl plus 2 g?L-1 KCl in drinking water for 4 weeks. Blood pressure was measured and,urine was collected for measurement of volume(UV),UNaV,UClV,UKV,UCaV and pH values,once a week. SGPT,CREA,SUGA,TRIG,CHOL,INS,ALD,ADH were measured in circulating blood samples. Kidney morphological changes and Na+,K+-ATPase activity of the renal tubular epithelial cells were also examined. Results Blood pressure,UV,UNaV and UClV were increased and histopathological changes of the kidney such as glomerulus sclerosis and tubular pachynsis were observed in the DOCA-Salt rats. Whereas UKV,UCaV,urine pH values,SGPT,CREA,SUGA,TRIG,CHOL,INS,ALD and ADH were not changed. In contrast,Na+,K+-ATPase activity of the renal tubular epithelial cells was decreased. Conclusion DOCA-Salt is a reliable hypertensive model with sodium retention.