Biomedical subjects

Juan Manuel Moreno

Publications and source records attributed to Juan Manuel Moreno.

13 recordsLinked to original sources

PubMed2007

The endocrine system in chronic nitric oxide deficiency.

The experimental model of chronic inhibition of nitric oxide (NO) production has proven to be a useful tool to study cardiovascular and renal lesions produced by this type of hypertension, which are similar to those found in human hypertension. It also offers a unique opportunity to study the interaction of NO with the humoral systems, known to have a role in the normal physiology of vascular tone and renal function. This review provides a thorough and updated analysis of the interactions of NO with the endocrine system. There is special focus on the main vasoactive factors, including the renin-angiotensin-aldosterone system, catecholamines, vasopressin, and endothelin among others. Recent discoveries of crosstalk between the endocrine system and NO are also reported. Study of these humoral interactions indicates that NO is a molecule with ubiquitous function and that its inhibition alters virtually to all other known regulatory systems. Thus, hypothyroidism attenuates the pressor effect of NO inhibitor N-nitro-L-arginine methyl ester, whereas hyperthyroidism aggravates the effects of NO synthesis inhibition; the sex hormone environment determines the blood pressure response to NO blockade; NO may play a homeostatic role against the prohypertensive effects of mineralocorticoids, thyroid hormones and insulin; and finally, NO deficiency affects not only blood pressure but also glucose and lipid homeostasis, mimicking the human metabolic syndrome X, suggesting that NO deficiency may be a link between metabolic and cardiovascular disease.

Animals↗

PubMed2006

Effects of chronic treatment with 7-nitroindazole in hyperthyroid rats.

This study analyzed the contribution of neuronal nitric oxide synthase (nNOS) to the hemodynamic manifestations of hyperthyroidism. The effects on hyperthyroid rats of the chronic administration of 7-nitroindazole (7-NI), an inhibitor of nNOS, were studied. Six groups of male Wistar rats were used: control, 7-NI (30 mg.kg-1.day-1 by gavage), T(4)50, T(4)75 (50 or 75 microg thyroxine.rat-1.day-1, respectively), T(4)50+7-NI, and T(4)75+7-NI. All treatments were maintained for 4 wk. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, pulse pressure (PP), and HR were measured in conscious rats, and morphological, metabolic, plasma, and renal variables were determined. Expression of nNOS in the hypothalamus of T(4)75 and control rats was analyzed by Western blot analysis. The response of mean arterial pressure (MAP) to pentolinium (10 mg/kg iv) was used to evaluate the sympathetic contribution to BP in T(4)75 and T(4)75+7-NI rats. T(4) produced an increased hypothalamic nNOS expression and dose-related increases in blood pressure (BP), HR, and PP vs. control rats. 7-NI did not modify BP or any other hemodynamic variable in normal rats. However, 7-NI produced a marked reduction in BP, HR, PP, and food and water intake in both hyperthyroid groups and improved creatinine clearance in the T(4)75 group. Pentolinium produced a greater MAP decrease in the T(4)75+7-NI than in the T(4)75 group. In conclusion, administration of 7-NI attenuates the hemodynamic and metabolic manifestations of hyperthyroidism, suggesting that nNOS contributes to the hyperdynamic circulation of this endocrine disease by modulating sympathetic activity.

Animals↗

PubMed2006

Chronic nitric oxide blockade modulates renal Na-K-2Cl cotransporters.

OBJECTIVE: The Na-K-2Cl cotransporter (NKCC2 isoform) of the thick ascending limb of Henle's loop (TAL) plays an important role in renal sodium handling, and the vascular isoform (NKCC1) participates in the response to vasoconstrictors. Both isoforms appear to be regulated by nitric oxide. This study aimed to analyze the effect of chronic nitric oxide deficiency on tubular and vascular Na-K-2Cl cotransporters in kidney and their potential role in the development of N-nitro-L-arginine-methyl ester (L-NAME) hypertension. METHODS: Wistar rats were given L-NAME (vehicle, 10, 35 and 80 mg/100 ml drinking water) for 4 weeks. Blood pressure was measured by the tail-cuff method. NKCC2 activity was estimated as the bumetanide-sensitive Rb influx in fresh isolated TAL tubules. NKCC1-contractile function was estimated as the bumetanide-sensitive vasocontractile response to phenylephrine in isolated perfused kidneys. Acute effects of L-NAME and endothelium removal were also evaluated. NKCC2 and NKCC1 protein expression were assessed by western blot analysis. RESULTS: Chronic L-NAME administration increased, in a dose-dependent manner, both blood pressure and NKCC2 activity, and these changes significantly correlated (r2 = 0.89, P < 0.01). NKCC1-contractile activity decreased with the highest dose of L-NAME (80 mg/100 ml drinking water group) but it was not affected by acute nitric oxide blockade or endothelium removal. This 80 mg group showed increased NKCC2 expression in the renal medulla and decreased NKCC1 expression in aorta. CONCLUSIONS: Chronic nitric oxide deficiency stimulates tubular Na-K-2Cl cotransporter, suggesting that NKCC2 hyperactivity contributes to the inability to excrete sodium, and hence to the development of L-NAME hypertension. In contrast, L-NAME hypertension develops independently of vascular NKCC1-contractile activity.

Animals↗

PubMed2006

Vascular and renal function in experimental thyroid disorders.

This review focuses on the effects of thyroid hormones in vascular and renal systems. Special emphasis is given to the mechanisms by which thyroid hormones affect the regulation of body fluids, vascular resistance and, ultimately, blood pressure. Vascular function is markedly affected by thyroid hormones that produce changes in vascular reactivity and endothelial function in hyper- and hypothyroidism. The hypothyroid state is accompanied by a marked decrease in sensitivity to vasoconstrictors, especially to sympathetic agonists, alteration that may play a role in the reduced blood pressure of hypothyroid rats, as well as in the preventive effects of hypothyroidism on experimental hypertension. Moreover, in hypothyroid rats, the endothelium-dependent and nitric oxide donors vasodilation is reduced. Conversely, the vessels from hyperthyroid rats showed an increased endothelium-dependent responsiveness that may be secondary to the shear-stress induced by the hyperdynamic circulation, and that may contribute to the reduced vascular resistance characteristic of this disease. Thyroid hormones also have important effects in the kidney, affecting renal growth, renal haemodynamics, and salt and water metabolism. In hyperthyroidism, there is a resetting of the pressure-natriuresis relationship related to hyperactivity of the renin-angiotensin system, which contributes to the arterial hypertension associated with this endocrine disease. Moreover, thyroid hormones affect the development and/or maintenance of various forms of arterial hypertension. This review also describes recent advances in our understanding of thyroid hormone action on nitric oxide and oxidative stress in the regulation of cardiovascular and renal function and in the long-term control of blood pressure.

Animals↗

PubMed2005

Cardiac and renal antioxidant enzymes and effects of tempol in hyperthyroid rats.

This study evaluated the activity of cardiac and renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)] and whether chronic treatment with tempol, a cell membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism. Two experiments were performed. In experiment I, the following four groups of male Wistar rats were used: control group and three groups that received thyroxine (T4) at 10, 50, or 75 microg x rat(-1) x day(-1). In experiment II, tempol was orally administered (18 mg x kg(-1) x day(-1)) to control and T4-treated (75 microg x rat(-1) x day(-1)) rats. All treatments were maintained for 6 wk. Body weight, tail systolic blood pressure (BP), and heart rate were measured one time a week, and direct BP and morphological, metabolic, plasma, and renal variables were measured at the end of the experiment. Enzymatic activities were measured in renal cortex and medulla and right and left ventricles. In renal cortex, SOD activity was decreased in the T4-75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T4-treated groups. Activity of all antioxidant enzymes was reduced in left ventricle in T4-50 and T4-75 groups and in right ventricle in the T4-75 group. Tempol reduced BP, plasma malondialdehyde, and total urinary excretion of F2 isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did not improve cardiac hypertrophy, proteinuria, or creatinine clearance in hyperthyroid rats. In conclusion, the results obtained indicate that the activity of SOD, GPX, and GR in renal and cardiac tissues is decreased in hyperthyroidism and that antioxidant treatment with tempol ameliorates T4-induced hypertension.

Animals↗

PubMed2005

Effects of chronic inhibition of inducible nitric oxide synthase in hyperthyroid rats.

We hypothesized that nitric oxide generated by inducible nitric oxide synthase (iNOS) may contribute to the homeostatic role of this agent in hyperthyroidism and may, therefore, participate in long-term control of blood pressure (BP). The effects of chronic iNOS inhibition by oral aminoguanidine (AG) administration on BP and morphological and renal variables in hyperthyroid rats were analyzed. The following four groups (n = 8 each) of male Wistar rats were used: control group and groups treated with AG (50 mg.kg(-1).day(-1), via drinking water), thyroxine (T4, 50 microg.rat(-1).day(-1)), or AG + T4. All treatments were maintained for 3 wk. Tail systolic BP and heart rate (HR) were recorded weekly. Finally, we measured BP (mmHg) and HR in conscious rats and morphological, plasma, and renal variables. T(4) administration produced a small BP (125 +/- 2, P < 0.05) increase vs. control (115 +/- 2) rats. AG administration to normal rats did not modify BP (109 +/- 3) or any other hemodynamic variable. However, coadministration of T4 and AG produced a marked increase in BP (140 +/- 3, P < 0.01 vs. T4). Pulse pressure and HR were increased in both T4- and T4 + AG -treated groups without differences between them. Plasma NOx (micromol/l) were increased in the T4 group (10.02 +/- 0.15, P < 0.05 vs. controls 6.1 +/- 0.10), and AG reduced this variable in T4-treated rats (6.81 +/- 0.14, P < 0.05 vs. T4) but not in normal rats (5.78 +/- 0.20). Renal and ventricular hypertrophy and proteinuria of hyperthyroid rats were unaffected by AG treatment. In conclusion, the results of the present paper indicate that iNOS activity may counterbalance the prohypertensive effects of T4.

Animals↗

PubMed2005

Antioxidant enzymes and effects of tempol on the development of hypertension induced by nitric oxide inhibition.

BACKGROUND: This study analyzed whether hypertension induced by N(omega)-nitro-l-arginine methyl ester (L-NAME) is associated with dysregulation of the main antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase [GPX], and glutathione reductase [GR]) and whether chronic administration of tempol ameliorates this hypertension. METHODS: Four groups of male Wistar rats were used: 1) control rats; 2) rats treated with L-NAME (35 mg/100 mL in drinking fluid); 3) rats treated with tempol (18 mg/100 mL in drinking fluid); and 4) rats treated with L-NAME plus tempol. All treatments were maintained for 6 weeks. Body weight, systolic blood pressure (BP) determined by the tail-cuff method, and heart rate were measured once per week. At the end of the experimental period, direct BP and morphologic, metabolic, plasma, and renal variables were measured. Enzymatic activities were measured in the kidney (cortex and medulla) and heart (right and left ventricles). RESULTS: Rats with L-NAME-induced hypertension showed increased copper-zinc (Cu-Zn) SOD activity in the renal cortex and medulla and the left and right ventricles, which was reduced by tempol administration. The manganese (Mn) SOD activity was increased by L-NAME and reduced by tempol in the renal cortex but was unchanged in other tissues. Catalase activity was not affected by L-NAME or tempol treatments in any tissue. Both GPX and GR activities were increased by L-NAME and reduced by tempol in the renal cortex and medulla but were not affected in the ventricles. Tempol reduced BP and total urinary excretion of 8-hydroxy-2'-deoxyguanosine in L-NAME-treated animals but did not affect either variable in controls. CONCLUSIONS: We conclude that L-NAME-induced hypertension is associated with an upregulation of antioxidant SOD, GPX, and GR activities. Moreover, the results indicate that tempol attenuates hypertension on nitric oxide-deficient rats and that oxidative stress participates in the established phase of this type of hypertension.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2004

Gender difference in the role of endothelium-derived relaxing factors modulating renal vascular reactivity.

UNLABELLED: This study analyzed the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in gender differences in the renal vascular reactivity of rats. Renal responses to vasoconstrictors and vasodilators were studied in isolated kidneys from male and female rats under basal conditions, after NO and EDHF blockade or after endothelium removal. Female rat kidneys had reduced responsiveness to vasoconstrictors. The blockade of NO or of EDHF did not completely abolish the differences, but the simultaneous blockade of both factors or endothelium removal abolished gender differences. Male and female kidneys showed a similar responsiveness to endothelium-dependent and -independent vasodilators under basal conditions and after NO or EDHF blockade. IN CONCLUSION: (a) the attenuated response to vasoconstrictors in female kidneys is related to an increased production of NO and EDHF; and (b), the contributions of NO and EDHF to endothelium-dependent vasodilation are similar in the male and female renal vasculature.

Animals↗

PubMed2004

Role of sex, gonadectomy and sex hormones in the development of nitric oxide inhibition-induced hypertension.

In this study we have evaluated the influence of sex, gonadectomy and sex hormones on the development of L-NAME-induced hypertension in the rat, focusing our investigation on blood pressure (BP), plasma renin activity (PRA), cardiac hypertrophy and proteinuria. Three experiments were performed to investigate: (i) the influence of sex on the development of L-NAME-induced hypertension; (ii) the effects of gonadectomy on the dimorphism of L-NAME-induced hypertension; and (iii) the effects of testosterone in ovariectomized female and of 17beta-oestradiol in orchidectomized male rats. Male L-NAME-treated rats had higher BP values than females. Orchidectomy of L-NAME-treated rats reduced BP to the levels of females and ovariectomy did not affect hypertension in females. Oestrogenized and orchidectomized males had a BP level similar to intact female L-NAME-treated rats. However, androgenization and ovariectomy did not change BP in female L-NAME-treated rats. PRA was greater in intact male L-NAME hypertensive rats than in female rats, and gonadectomy protected against the increase in PRA such that PRA was similar among all the groups. Intact female hypertensive rats showed significantly greater ventricular hypertrophy compared with male hypertensive rats. Male L-NAME hypertensive rats had increased proteinuria that was not present in female rats. Moreover, testosterone increased proteinuria in males and females regardless of the BP level. Male L-NAME-treated rats developed higher BP, PRA and proteinuria than female rats, but were more resistant to the development of cardiac hypertrophy. The higher PRA of male L-NAME-treated rats might be involved in the sex-dependent dimorphism of this model of hypertension.

Animals↗

PubMed2003

Increased pressor sensitivity to chronic nitric oxide deficiency in hyperthyroid rats.

We studied the effects of a possible interaction between partial nitric oxide deficiency and thyroid hormone excess on the long-term control of blood pressure (BP) and morphological and renal variables and examined the role of the renin-angiotensin system in the increased BP of this interaction. Eight groups (n=8 each) of male Wistar rats were used: a control group; 3 groups that were treated with thyroxine (50 microg/d), Nw-nitro-L-arginine methyl ester (L-NAME; subpressor dose, 1.5 mg x kg(-1) d(-1)), or thyroxine plus L-NAME; and another 4 similarly treated groups that received losartan (20 mg x kg(-1) x d(-1)) in their drinking fluid. All treatments were maintained for 3 weeks. The time course of tail systolic BP was recorded once a week. At the end of the experimental period, we measured mean arterial pressure in conscious rats and assessed the morphological, metabolic, plasma, and renal variables. Thyroxine produced a mild BP increase from the second week of treatment and an increase in plasma angiotensin II and plasma nitrates/nitrites by the end of the study. Simultaneous administration of thyroxine and a subpressor dose of L-NAME produced a marked BP increase that reached significance from the first week of treatment. Losartan produced normotension in thyroxine-treated rats and attenuated the BP elevation in thyroxine+L-NAME-treated rats. Hyperthyroid rats showed relative renal and ventricular hypertrophy, absence of absolute left ventricular hypertrophy, and proteinuria. These alterations were not changed by losartan. We conclude that an impaired nitric oxide system might have a counterregulatory homeostatic role against the prohypertensive effects of thyroid hormone and that the renin-angiotensin system plays an important role in thyroxine+L-NAME hypertension.

Angiotensin II↗

PubMed2003

Role of endothelium-derived relaxing factors in the renal response to vasoactive agents in hypothyroid rats.

This study analyzed the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in the abnormal renal vascular reactivity of hypothyroid rats. Renal responses to vasoconstrictors [VC: phenylephrine (PHE) and ANG II] and vasodilators [VD: ACh, sodium nitroprusside (SNP), and papaverine (PV)] were studied in kidneys from control and hypothyroid rats under normal conditions and after NO or EDHF blockade. NO was blocked by the administration of Nomega-nitro-l-arginine methyl ester (l-NAME) and EDHF by the administration of tetraethylammonium (TEA) or by an increased extracellular K+. The response to VC was also evaluated after endothelium removal. Hypothyroid kidneys showed reduced responsiveness to PHE and a normal response to ANG II. l-NAME and TEA administration produced an increased sensitivity to PHE and to ANG II in control preparations. l-NAME also increased the response to PHE in hypothyroid kidneys, but the differences between control and hypothyroid kidneys were maintained. TEA administration did not change the response to either VC in hypothyroid preparations. In endothelium-removed preparations, TEA was unable to increase pressor responsiveness to VC. Hypothyroid kidneys showed reduced responsiveness to ACh and SNP and normal response to PV. The differences between hypothyroid and control preparations in the responses to ACh and SNP were maintained after l-NAME or increased K+. In conclusion, this study shows that 1) the attenuated response to PHE in hypothyroidism is not related to an increased production of endothelium-derived relaxing factors NO and EDHF; 2) the response to VC in hypothyroid preparations is insensitive to EDHF blockade; and 3) hypothyroid preparations have a reduced reactivity to the NO donor, and NO-independent vasodilatation remains unaffected.

Angiotensin II↗

PubMed2003

Chronic blockade of neuronal nitric oxide synthase does not affect long-term control of blood pressure in normal, saline-drinking or deoxycorticosterone-treated rats.

It has been reported that long-term selective inhibition of neuronal nitric oxide synthase (nNOS) produces elevated blood pressure (BP) in normal rats. The present study was designed to analyse the possible influences of the sodium-retaining hormone deoxycorticosterone acetate (DOCA) and of an increased sodium intake on BP effects induced by the chronic blockade of nNOS with 7-nitroindazole (7NI). Two experiments were performed using 7NI at a dose of either 10 mg x kg(-1) x day(-1) (experiment 1) or 30 mg x kg(-1) x day(-1) (experiment 2). The following groups were used in both experiments: control rats, and rats that received either 1 % saline drinking water (Salt), deoxycorticosterone acetate (DOCA), 7NI, 7NI plus 1 % saline (7NI + Salt) or 7NI plus DOCA (7NI + DOCA). The tail systolic BP (SBP) was measured in all rats once a week. At the end of the experimental period, the mean arterial pressure (MAP) and metabolic, morphological and renal variables were measured. There were no significant differences in the tail SBP, final MAP or glomerular filtration rate between the experimental groups and the control group. In both experiments, the plasma renin activity (PRA) was significantly inhibited in the Salt groups and suppressed in the DOCA groups. The PRA significantly increased in the 7NI groups, whereas the 7NI + Salt and 7NI + DOCA groups showed a significant inhibition in PRA, especially compared to the 7NI groups in the two experiments. We conclude that chronic nNOS blockade is unable to increase BP in normal, saline-drinking or DOCA-treated rats. Furthermore, the nNOS blockade does not interfere with the counterbalance between renin and an increased sodium intake or retention.

Angiotensin I↗

PubMedDate not supplied

Hardware optimization and serial implementation of a novel spiking neuron model for the POEtic tissue.

In this paper we describe the hardware implementation of a spiking neuron model, which uses a spike time dependent plasticity (STDP) rule that allows synaptic changes by discrete time steps. For this purpose an integrate-and-fire neuron is used with recurrent local connections. The connectivity of this model has been set to 24 neighbours, so there is a high degree of parallelism. After obtaining good results with the hardware implementation of the model, we proceed to simplify this hardware description, trying to keep the same behaviour. Some experiments using dynamic grading patterns have been used in order to test the learning capabilities of the model. Finally, the serial implementation has been realized.

Action Potentials↗