Improvement of the cardiovascular effect of methyldopa by complexation with Zn(II): Synthesis, characterization and mechanism of action.

BACKGROUND: the antihypertensive drug α-methyldopa (MD) stands as one of the extensively used medications for managing hypertension during pregnancy. Zinc deprivation has been associated with many diseases. In this context, the synthesis of a Zn coordination complex [Zn(MD)(OH)(H2O)2]·H2O (ZnMD) provide a promising alternative pathway to improve the biological properties of MD. METHODS: ZnMD was synthesized and physicochemically characterized. Fluorescence spectral studies were conducted to examine the binding of both, the ligand and the metal with bovine serum albumin (BSA). MD, ZnMD, and ZnCl2 were administered to spontaneous hypertensive rats (SHR) rats during 8 weeks and blood pressure and echocardiographic parameters were determined. Ex vivo assays were conducted to evaluate levels of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), and nitric oxide (NO). Cross-sectional area (CSA) and collagen levels of left ventricular cardiomyocytes were also assessed. Furthermore, the expression of NAD(P)H oxidase subunits (gp91phox and p47phox) and Superoxide Dismutase 1 (SOD1) was quantified through western blot analysis. RESULTS: The complex exhibited a moderate affinity for binding with BSA showing a spontaneous interaction (indicated by negative ΔG values) and moderate affinity (determined by affinity constant values). The binding process involved the formation of Van der Waals forces and hydrogen bonds. Upon treatment with MD and ZnMD, a reduction in the systolic blood pressure in SHR was observed, being ZnMD more effective than MD (122 ± 8.1 mmHg and 145 ± 5.6 mmHg, at 8th week of treatment, respectively). The ZnMD treatment prevented myocardial hypertrophy, improved the heart function and reduced the cardiac fibrosis, as evidenced by parameters such as left ventricular mass, fractional shortening, and histological studies. In contrast, MD did not show noticeable differences in these parameters. ZnMD regulates negatively the oxidative damage by reducing levels of ROS and lipid peroxidation, as well as the cardiac NAD(P)H oxidase, and increasing SOD1 expression, while MD did not show significant effect. Moreover, cardiac nitric oxide levels were greater in the ZnMD therapy compared to MD treatment. CONCLUSION: Both MD and ZnMD have the potential to be transported by albumin. Our findings provide important evidence suggesting that this complex could be a potential therapeutic drug for the treatment of hypertension and cardiac hypertrophy and dysfunction.

Different culture media containing methyldopa for melanin production by Cryptococcus species.

INTRODUCTION: Melanin production by species of Cryptococcus is widely used to characterize C. neoformans complex in mycology laboratories. This study aims to test the efficacy of methyldopa from pharmaceutical tablet as a substrate for melanin production, to compare the production of melanin using different agar base added with methyldopa, and to compare the melanin produced in those media with that produced in Niger seed agar and sunflower seed agar by C. neoformans, C. laurentii, and C. albidus. Two isolates of each species, C. neoformans, C. laurentii, and C. albidus, and one of Candida albicans were used to experimentally detect conditions for melanin production. METHODS: The following media were tested: Mueller-Hinton agar (MHA), brain and heart infusion agar (BHIA), blood agar base (BAB), and minimal medium agar (MMA), all added with methyldopa, and the media Niger seed agar (NSA) and sunflower seed agar (SSA). RESULTS: All isolates grew in most of the culture media after 24h. Strains planted on media BAB and BHIA showed growth only after 48h. All isolates produced melanin in MMA, MHA, SSA, and NSA media. CONCLUSIONS: Methyldopa in the form pharmaceutical tablet can be used as a substrate for melanin production by Cryptococcus species; minimal medium plus methyldopa was more efficient than the BAB, MHA, and BHIA in the melanin production; and NSA and SSA, followed by MMA added with methyldopa, were more efficient than other media studied for melanin production by all strains studied.

Different culture media containing methyldopa for melanin production by Cryptococcus species / Avaliação de diferentes meios de cultura contendo metildopa para a produção de melanina por espécies de Cryptococcus

INTRODUCTION: Melanin production by species of Cryptococcus is widely used to characterize C. neoformans complex in mycology laboratories. This study aims to test the efficacy of methyldopa from pharmaceutical tablet as a substrate for melanin production, to compare the production of melanin using different agar base added with methyldopa, and to compare the melanin produced in those media with that produced in Niger seed agar and sunflower seed agar by C. neoformans, C. laurentii, and C. albidus. Two isolates of each species, C. neoformans, C. laurentii, and C. albidus, and one of Candida albicans were used to experimentally detect conditions for melanin production. METHODS: The following media were tested: Mueller-Hinton agar (MHA), brain and heart infusion agar (BHIA), blood agar base (BAB), and minimal medium agar (MMA), all added with methyldopa, and the media Niger seed agar (NSA) and sunflower seed agar (SSA). RESULTS: All isolates grew in most of the culture media after 24h. Strains planted on media BAB and BHIA showed growth only after 48h. All isolates produced melanin in MMA, MHA, SSA, and NSA media. CONCLUSIONS: Methyldopa in the form pharmaceutical tablet can be used as a substrate for melanin production by Cryptococcus species; minimal medium plus methyldopa was more efficient than the BAB, MHA, and BHIA in the melanin production; and NSA and SSA, followed by MMA added with methyldopa, were more efficient than other media studied for melanin production by all strains studied.

INTRODUÇÃO: A produção de melanina por espécies de Cryptococcus é uma característica amplamente utilizada em laboratórios de micologia para caracterização do complexoC. neoformans. O objetivo deste estudo foi verificar a eficácia da metildopa na forma farmacêutica de comprimido, como substrato para a produção de melanina por Cryptococcus, comparar diferentes bases de meios de cultura acrescidas de metildopa para produção de melanina e comparar o pigmento produzido nestes meios com o produzido em ágar Níger e ágar girassol por C. neoformans, C. laurentii e C. albidus. MÉTODOS: Foram testados dois isolados de cada uma das espécies, C. neoformans, C.laurentii e C.albidus, e um de C. albicans para avaliar a produção de melanina nos meios de cultura ágar Müeller-Hinton (MH), ágar brain heart infusion (BHI), ágar base sangue (BS), meio mínimo (MM), todos acrescidos de metildopa, e ainda ágar girassol e ágar Níger. RESULTADOS: Todos os isolados cresceram na maioria dos meios após 24h. O crescimento nos meios BS e BHI somente ocorreu após 48h. Todos os isolados produziram melanina nos meios MM, MH, girassol e Niger. CONCLUSÕES: A metildopa de origem farmacêutica pode ser utilizada como substrato para a produção de melanina por espécies de Cryptococcus; o MM acrescido de metildopa mostrou-se mais eficiente na produção de melanina do que os meios BS, MH e BHI; ágar girassol e ágar Níger seguidos de MM acrescido de metildopa foram os mais eficientes na produção de melanina pelos isolados estudados.

Molecular phylogeny of the subgenus Drosophila (Diptera, Drosophilidae) with an emphasis on Neotropical species and groups: a nuclear versus mitochondrial gene approach.

The genus Drosophila has played an essential role in many biological studies during the last 100 years but much controversy and many incompletely addressed issues still remain to be elucidated regarding the phylogeny of this genus. Because information on the Neotropical species contained in the subgenus Drosophila is particularly incomplete, with this taxonomic group being underrepresented in many studies, we designed a study to answer some evolutionary questions related to these species. We subjected at least 41 Drosophilidae taxa to a phylogenetic analysis using a 516-base pair (bp) fragment of the alpha-methyldopa (Amd) nuclear gene and a 672 bp fragment of the mitochondrial cytochrome oxidase subunit II (COII) gene both individually and in combination. We found that the subgenus Drosophila is paraphyletic and subdivided into two main clusters: the first containing species traditionally placed in the virilis-repleta radiation and the second assembling species of the immigrans-Hirtodrosophila radiation. Inside the first of these clusters we could detect the monophyly of both the flavopilosa (the sister-clade of the annulimana group) and the mesophragmatica (closely related to the repleta group) species groups. Concerning the immigrans-Hirtodrosophila lineage, Zaprionus, Liodrosophila, Samoaia, and Hirtodrosophila were the early offshoots, followed by the immigrans, quinaria, testacea, and funebris species groups. The tripunctata radiation appears to be a derived clade, composed of a paraphyletic tripunctata group, intimately interposed with members of the cardini, guarani, and guaramunu species groups. Overall, the COII gene yielded a poor phylogenetic performance when compared to the Amd gene, the evolutionary hypothesis of which agreed with the total evidence tree. This phenomenon can be explained by the fast saturation of transitional substitutions in COII, due to strong biases in both base composition and substitution patterns, as also by its great among-site rate variation heterogeneity.

Pharmacokinetic profile of methyldopa in the brain of sinaortic-denervated rats.

Pharmacokinetics of methyldopa (MD) and the effect on the dopaminergic metabolism was studied in anesthetized sham-operated (SO) and sinoaortic-denervated (SAD) rats by using the microdialysis technique. A concentric microdialysis probe was placed in the striatum or in the posterior hypothalamus. Levels of MD, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured by high pressure liquid chromatography coupled to electrochemical detection (HPLC-EC). Following the i.p. administration of MD (50 mg x kg(-1), i.p.), striatal dialysates showed that this drug rapidly reaches the brain. However, in SAD rats the MD levels of dialysates were lower and decreased more rapidly compared to SO rats. On the other hand, dialysates of posterior hypothalamus showed that in SAD animals the accumulation of MD was significantly greater than in SO rats.MD does not significantly reduce the striatal production of dopaminergic metabolite DOPAC in both groups of rats. The drug also induces a decrease of DOPAC levels in hypothalamic dialysates of SO and SAD animals. On the other hand, a no significative decay of HVA levels was seen in the striatal dialysate of both groups of experimental animals. In conclusion, this study by using a microdialysis technique shows that MD has different kinetic profiles in dialysates from posterior hypothalamus and striatum of SO and SAD rats at a dose that alters dopaminergic metabolism.

Pharmacokinetic and pharmacodynamic alterations of methyldopa in rats with aortic coarctation. A study using microdialysis.

A pharmacokinetic-pharmacodynamic study of methyldopa (MD) was made in anesthetized sham operated (SO) and aortic coarctated (ACo) rats by using a vascular shunt probe for arterial microdialysis and simultaneous blood pressure recording. Anesthetized Wistar rats were used 7 days after aortic coarctation or sham operation. A vascular shunt probe was inserted into the carotid artery and a concentric probe was placed into the striatum or posterior hypothalamus. MD and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in the dialysates by HPLC-EC. MD (50 mg kg(-1)i.p.) induced an increase of heart rate in SO (Delta HR: 108 +/- 22 bpm, n= 6) and in ACo rats (Delta HR: 55 +/- 10 bpm, n= 6, P< 0.05, one way ANOVA). Moreover, MD also reduced the mean arterial pressure (MAP) of SO rats (Delta MAP: -10 +/- 4 mmHg, n= 6) and ACo animals (Delta MAP: -51 +/- 9 mmHg, n= 6, P< 0.05, one way ANOVA). Analysis of the arterial blood dialysates showed a lower half-life of MD in ACo rats (t(1/2): 1.5 +/- 0.3 h, n= 6, P< 0.05, 't' test) than in SO rats (t(1/2): 3.7 +/- 1.0 h, n= 6). A low accumulation and a fast decay of striatal MD levels were seen in ACo rats. However, peak levels of drug were greater in the hypothalamic dialysates of ACo rats than in SO animals samples. On the other hand, MD also induced an increase of DOPAC levels in the hypothalamic dialysates of ACo rats. In conclusion, the aortic coarctation modifies the pharmacokinetic and cardiovascular effect of MD in the rat. The action of this drug on dopaminergic neurotransmission is also altered in the ACo animals.

The effects of nitric oxide synthase inhibitors on the sedative effect of clonidine.

UNLABELLED: The mechanism underlying the Niteroi, Rio de Janeiro sedative effect of clonidine, an alpha2-adrenoceptor agonist, remains uncertain. Because activation of alpha2-adrenoceptors induces release of nitric oxide (NO), we tested the hypothesis that the sedative effect of clonidine depends on NO-related mechanisms. The effect of 7-nitro indazole on the sleeping time induced by clonidine was studied in Wistar rats. In addition, we examined the effect of clonidine, alpha-methyldopa, and midazolam on the thiopental-induced sleeping time in rats pretreated with N(G)-nitro-L-arginine-methyl-ester (L-NAME). The sleeping time induced by clonidine was significantly decreased by 7-nitro indazole. Thiopental sleeping time was increased by clonidine, alpha-methyldopa, and midazolam. L-NAME reduced the prolongation effect of clonidine and alpha-methyldopa, but did not alter the effect of midazolam on the thiopental-induced sleeping time. The inhibitory effect of L-NAME on clonidine-dependent prolongation of thiopental-induced sleeping time was reversed by L-arginine. These results suggest that NO-dependent mechanisms are involved in the sedative effect of clonidine. In addition, this effect seems to be specific for the sedative action of alpha2-adrenoceptors agonists. IMPLICATIONS: Clonidine, an antihypertensive drug, is also a sedative. This sedative effect, although an adverse event in the treatment of hypertensive patients, can be helpful for sedation of surgical patients. The mechanism of this effect, however, is unknown. In this study, we show that the sedative effect of clonidine is mediated by nitric oxide, because it could be prevented by pretreatment with nitric oxide synthase inhibitors.

Study of the evolution of blood and striatal levels of methyldopa: a microdialysis study in sinaortic denervated rats.

Pharmacokinetic of methyldopa (50 mg kg(-1)i.p.) was studied in anesthetized sham operated and sinoaortic denervated (SAD) rats by using the microdialysis technique. Vascular shunt probe was inserted into the carotid artery and concentric probe was placed in the striatum. Levels of methyldopa were measured by HPLC-EC. The number of animals in each group was six and normal distribution of the variables of the study was assumed. Peak concentrations in arterial blood of methyldopa were similar in both groups of rats but the elimination rate constant was 0.31+/-0.09 h(-1)for sham rats (n =6) and 1.28+/-0.31 h(-1)for SAD rats (n =6, P<0.05). Low levels of methyldopa and a more pronounced decrease were seen in striatum of sinoaortic denervated rats. In conclusion, by using a microdialysis technique, different kinetic profiles of methyldopa were observed in sham operated and sinoaortic denervated rats.

Lack of involvement of the kallikrein-kinin system in the depressor effect of alpha-methyldopa in normotensive rats.

1. We evaluated the involvement of circulating kinins in the hypotensive effect of the antihypertensive drug alpha-methyldopa (alpha-MD) in normotensive rats. 2. The alpha-MD effects were more pronounced in urethane-anesthetized rats than in unanesthetized animals. 3. Treatment with alpha-MD did not affect the circulating levels of kininogen, the bradykinin precursor. 4. Pretreatment with captopril that potentiates the depressor effects of bradykinin did not potentiate the hypotension to alpha-MD. 5. The lack of changes in kininogen levels and the failure of captopril to potentiate the depressor effects of alpha-MD rules out an involvement of the circulating kallikrein-kinin system in the response to alpha-MD.

Effects of the antihypertensive drugs alpha-methyldopa and hydralazine on the performance of spontaneously hypertensive rats in the elevated plus-maze.

The effects of antihypertensive drugs on the performance of spontaneously hypertensive rats (SHR) in the elevated plus-maze were determined. Male SHR (3 months old) were submitted to long-term treatment (15 days) with alpha-methyldopa (alpha MD, 5 g/l, N = 10) and hydralazine (HYD, 100 mg/l, N = 10) given orally, diluted in water. After the drug treatment, the performance of the rats in the plus-maze was observed for 5 min in a single test and mean arterial pressure (MAP) and heart rate (HR) were then measured. The antihypertensive drugs reduced MAP significantly (mean +/- SEM: CON = 176.2 +/- 5.2, alpha MD = 157.8 +/- 4.6 and HYD = 150 +/- 4.4 mmHg) and only alpha MD increased HR significantly (mean +/- SEM: CON = 391.7 +/- 13.8, alpha MD = 453.3 +/- 14 and HYD = 368.8 +/- 18.9 bpm). The alpha MD group presented a lower total number of entries (mean +/- SEM: CON = 12.7 +/- 0.7, alpha MD = 8.7 +/- 0.9 and HYD = 12 +/- 0.9) and spent less time in the open arms than the CON (N = 10) and HYD groups (mean +/- SEM: CON = 0.69 +/- 0.04, alpha MD = 0.48 +/- 0.07 and HYD = 0.65 +/- 0.06 s). alpha-Methyldopa acts centrally and hydralazine acts peripherally. The behavioral change of SHR treated with alpha-methyldopa suggests that hypertension seems to be related to central nervous dysfunctions that are affected by an antihypertensive drug with central noradrenergic action.

In vitro study of the effect of clonidine on human umbilical artery motility.

The umbilical-placental circulation is of vital importance for fetal survival and has a dominant effect on the cardiorespiratory physiology of the fetus. The mechanisms of regulation of umbilical vessels appear to differ from those regulating other vessels. Both clonidine and alpha-methyldopa have been used in the management of hypertensive complications of pregnancy. In contrast to alpha-methyldopa, clonidine does not require previous metabolization but acts directly on the receptors. The action of the two drugs on human umbilical artery was studied in vitro. Forty-eight human umbilical artery segments were dissected and perfused as follows: 9 segments with alpha-methyldopa, 10 with clonidine, 10 with yohimbine, 9 with alpha-methyldopa in combination with yohimbine, and 10 with pure Tyrode's solution. alpha-Methyldopa had a statistically significant vasoconstrictive effect starting at 40 min (p < 0.05) and this effect was blocked by yohimbine (p < 0.05). Clonidine had no vasoconstrictive effect. The present data for clonidine do not confirm the presence of alpha 2-adrenergic receptors in the umbilico-placental circulation which had been indicated by the action of methyldopa.

Effects of the antihypertensive drugs Ó-methyldopa and hydralazine on the performance of spontaneously hypertensive rats in the elevated plus-maze

The effects of antihypertensive drugs on the performance of spontaneously hypertensive rats (SHR) in the elevated plus-maze were determined. Male SHR (3 months old) were submitted to long-term treatment (15 days) with Ó-methyldopa (ÓMD, 5g/l, N = 10) and hydralazine (HYD, 100 mg/l, N = 10) given orally, diluted in water. After the drug treatment, the performance of the rats in the plus-maze was observed for 5 min in a single test and mean arterial pressure (MAP) and heart rate (HR) were then measured. The antihypertensive drugs reduced MAP significantly (mean ñ SEM:CON = 176.2 ñ 5.2, ÓMD = 157.8 ñ 4.6 and HYD = 150 ñ 4.4 mmHg) and only ÓMD increased HR significantly (mean ñ SEM:CON = 391.7 ñ 13.8, ÓMD = 453.3 ñ 14 and HYD = 368.8 ñ 18.9 bpm). The ÓMD group presented a lower total number of entries (mean ñ SEM:CON = 12.7 ñ 0.7, ÓMD = 8.7 ñ 0.9 and HYD = 12 ñ 0.9) and spent less time in the open arms than the CON (N = 10) and HYD groups (mean ñ SEM:CON = 0.69 ñ 0.04, ÓMD = 0.48 ñ 0.07 and HYD = 0.65 ñ 0.06 s). ÓMethyldopa acts centrally and hydralazine acts peripherally. The behavioral change of SHR treated with Ó-methyldopa suggests that hypertension seems to be related to central nervous dysfunctions that are affected by an antihypertensive drug with central noradrenergic action

Action of alpha-methyldopa on human umbilical circulation in vitro.

To determine the possible effects of alpha-methyldopa on the motility of human umbilical artery, a total of 53 arterial segments were perfused with different concentrations of the drug as follows: 38 segments with 125, 250 and 500 ng/ml of the drug, 9 segments with 500 ng/ml alpha-methyldopa in combination with 10(-7) M yohimbine, and 6 segments with 10(-7) M yohimbine alone. alpha-Methyldopa had a vasoconstrictor effect at all doses employed, with a clear dose-effect correlation (p less than 0.01). The vasoconstrictor effect of 500 ng/ml alpha-methyldopa was fully inhibited in the presence of 10(-7) M yohimbine. These results suggest that alpha 2-adrenergic receptors are present in the umbilical circulation and that alpha-methyldopa may play a role in the control of this circulation.

[Effect of alpha methyldopa on heart in renovascular hypertension]. / Efecto de la alfa metildopa sobre el corazón en la hipertensión renovascular.

Previous studies from our laboratory, have demonstrated that 21 days after unclipping the decrease in arterial pressure (AP) was followed by a regression of cardiac hypertrophy (CH) and a normalization of contractile response to Isoproterenol (I) stimulation in two kidney one clip (2K1C) hypertension. The purpose in this study was to reexamine the effects of Alpha Methyl Dopa (AMD) treatment on AP, CH and cardiac response to I stimulation in this model. A total of 43 male rats, ten weeks old, were used. In 19 rats a silver clip was placed under ether anaesthesia in the left renal artery (clip group) (K). The remaining 24 animals constituted the control group (C). Twenty one days later, in 9 and in 17 animals from K and C groups, treatment with AMD 100 mg/kg/day per os was started and maintained during the three week-follow-up period (K alpha and C alpha groups). AP was measured twice a week by the tail cuff method and body weight was registered once a week. We defined hypertension when the systolic pressure was 150 mmHg or more. Three weeks after clipping and 21 days after treatment, in the clipped animals, simultaneously with matched controls (C alpha and K alpha) the cardiac response to Isoproterenol stimulation was studied. For this purpose, under pentobarbital anesthesia the carotid artery and the femoral artery and vein were cannulated in order to measure mean arterial pressure (MAP), left ventricular systolic pressure, heart rate (HR) and DP/DT+ Max in basal conditions and after I (0.001, 0.02, 0.04, 0.12 and 0.24 microgram/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Efecto de la alfa metildopa sobre el corazón en la hipertensión renovascular / Effect of alpha methyldopa on heart in renovascular hypertension

Resultados previos mostraron que la hipertrofia cardíaca (HC) y la respuesta contráctil al Isoproterenol (I) en el modelo 2R Ic, se normalizagba tres semanas sdespués del descenso de la presión arterial (PA) por el declipado de la arteria renal. En el presente trabajo se estudió el efecto de la Alfa Metidopa (aMD) sobre la PA, HC y la respuesta al I. Con ese propósito, a 43 ratas macho Wistar, de 280 gramos, se las dividió en: a) Grupo Control (C) (n = 24). Luego de tres semanas de control de PA, a 17 de ellas se les administró aMD per os a la dosis de 100 mg/kg/día durante 21 días (C alta). b) Grupo clip (K) (n = 19), a los que se les colocó un clip de plata en la arteria renal izquierda. Luego de tres semanas de hipertensión a (n = 9) (K alfa) se les administró aMD en forma similar a C Alfa. La respuesta al I se evaluó a los 21 a C y K y a los 42 días a C alfa y K alfa. A tal fin, previa anestesia se canularon la carótida, la arteria y vena femorales y se registró la frecuencia cardíaca (FC), la presión arterial media (PAM), la presión sistólica y diastólica de ventrículo izquierdo y la DP/DT + MAX en condiciones basales, y luego de dosis unicas crecientes de I. Al finalizar la experiencia se determinó el peso biventricular (PC) y se normalizó por el peso corporal (pc). La PA aumentó en K (p < 0,05): 179 ñ 2,3 vs C 125 ñ 2,9 y con aMD descendió: C alfa 111 + 2,5 y K alfa 151,7 ñ 6 (p < 0,05). EIPC (g) con aMD fue menor en C alfa (p < 0,05) 0,69 ñ 0,04 vs 0,78 ñ 0,05 y en K alfa...(AU)

Efecto de la alfa metildopa sobre el corazón en la hipertensión renovascular / Effect of alpha methyldopa on heart in renovascular hypertension

Resultados previos mostraron que la hipertrofia cardíaca (HC) y la respuesta contráctil al Isoproterenol (I) en el modelo 2R Ic, se normalizagba tres semanas sdespués del descenso de la presión arterial (PA) por el declipado de la arteria renal. En el presente trabajo se estudió el efecto de la Alfa Metidopa (aMD) sobre la PA, HC y la respuesta al I. Con ese propósito, a 43 ratas macho Wistar, de 280 gramos, se las dividió en: a) Grupo Control (C) (n = 24). Luego de tres semanas de control de PA, a 17 de ellas se les administró aMD per os a la dosis de 100 mg/kg/día durante 21 días (C alta). b) Grupo clip (K) (n = 19), a los que se les colocó un clip de plata en la arteria renal izquierda. Luego de tres semanas de hipertensión a (n = 9) (K alfa) se les administró aMD en forma similar a C Alfa. La respuesta al I se evaluó a los 21 a C y K y a los 42 días a C alfa y K alfa. A tal fin, previa anestesia se canularon la carótida, la arteria y vena femorales y se registró la frecuencia cardíaca (FC), la presión arterial media (PAM), la presión sistólica y diastólica de ventrículo izquierdo y la DP/DT + MAX en condiciones basales, y luego de dosis unicas crecientes de I. Al finalizar la experiencia se determinó el peso biventricular (PC) y se normalizó por el peso corporal (pc). La PA aumentó en K (p < 0,05): 179 ñ 2,3 vs C 125 ñ 2,9 y con aMD descendió: C alfa 111 + 2,5 y K alfa 151,7 ñ 6 (p < 0,05). EIPC (g) con aMD fue menor en C alfa (p < 0,05) 0,69 ñ 0,04 vs 0,78 ñ 0,05 y en K alfa...

Prevalence of drug-induced immunologic changes in hypertensive Jamaicans.

Of 137 hypertensive black Jamaicans who took methyldopa for a mean period of 36 months, a positive ANA was found in 1.5% and a positive direct Coombs' test in 0.7%. In 36 patients in whom hydralazine was included in the therapeutic regimen, a positive ANA was seen in only 6%. These results suggest that in black populations, immunologic abnormalities induced by antihypertensive drugs are less common than has been reported in white patients.