Examinando por Autor "Banegas, Inmaculada"

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Aminopeptidase Activities Interact Asymmetrically between Brain, Plasma and Systolic Blood Pressure in Hypertensive Rats Unilaterally Depleted of Dopamine
(BIOMEDICINES, 2022) Banegas, Inmaculada; Prieto-Gómez, María Isabel; Segarra, Ana Belén; Vives, Francisco; Martínez-Cañamero, Magdalena; Durán, Raquel; Luna, Juan Dios; Domínguez-Vías, Germán; Ramírez-Sánchez, Manuel
Brain dopamine, in relation to the limbic system, is involved in cognition and emotion. These functions are asymmetrically processed. Hypertension not only alters such functions but also their asymmetric brain pattern as well as their bilateral pattern of neurovisceral integration. The central and peripheral renin-angiotensin systems, particularly the aminopeptidases involved in its enzymatic cascade, play an important role in blood pressure control. In the present study, we report how these aminopeptidases from left and right cortico-limbic locations, plasma and systolic blood pressure interact among them in spontaneously hypertensive rats (SHR) unilaterally depleted of dopamine. The study comprises left and right sham and left and right lesioned (dopamine-depleted) rats as research groups. Results revealed important differences in the bilateral behavior comparing sham left versus sham right, lesioned left versus lesioned right, and sham versus lesioned animals. Results also suggest an important role for the asymmetrical functioning of the amygdala in cardiovascular control and an asymmetrical behavior in the interaction between the medial prefrontal cortex, hippocampus and amygdala with plasma, depending on the left or right depletion of dopamine. Compared with previous results of a similar study in Wistar-Kyoto (WKY) normotensive rats, the asymmetrical behaviors differ significantly between both WKY and SHR strains.
Asymmetric interaction of neuropeptidase activities between cortico-limbic structures, plasma and cardiovascular function after unilateral dopamine depletions of the nigrostriatal system
(MDPI, 2022-02) Banegas, Inmaculada; Prieto-Gómez, María Isabel; Segarra, Ana Belén; Vives, Francisco; Martínez-Cañamero, Magdalena; Durán, Raquel; Luna, Juan Dios; de-Gasparo, Marc; Domínguez-Vías, Germán; Ramírez-Sánchez, Manuel
In emotional processing, dopamine (DA) plays an essential role, and its deterioration involves important consequences. Under physiological conditions, dopamine exhibits brain asymmetry and coexists with various neuropeptides that can coordinate the processing of brain functions. Brain asymmetry can extend into a broader concept of asymmetric neurovisceral integration, including behavior. The study of the activity of neuropeptide regulatory enzymes (neuropeptidases, NPs) is illustrative. We have observed that the left and right brain areas interact intra- and inter-hemispherically, as well as with peripheral tissues or with physiological parameters such as blood pressure or with behaviors such as turning preference. To obtain data that reflect this integrative behavior, we simultaneously analyzed the impact of left or right brain DA depletion on the activity of various NPs in corticolimbic regions of the left and right hemispheres, such as the medial prefrontal cortex, amygdala and hippocampus, as well as on the plasma activity of the same aminopeptidase activities (APs) and on systolic blood pressure (SBP). Intra- and inter-hemispheric interactions as well as the interactions of NPs from the left or right hemispheres were analyzed with the same plasma APs and the SBP obtained from sham and from left or right lesioned rats. The results demonstrate a complex profile depending on the hemisphere considered. They definitively confirm an asymmetric neurovisceral integration and reveal a higher level of inter-hemispheric corticolimbic interactions including with SBP after left dopamine depletion.
Asymmetric Pattern of Correlations of Leucine Aminopeptidase Activity between Left or Right Frontal Cortex versus Diverse Left or Right Regions of Rat Brains
(MDPI, 2023-07) Ramírez-Sánchez, Manuel; Prieto-Gómez, María Isabel; Segarra, Ana Belén; Banegas, Inmaculada; Martínez-Cañamero, Magdalena; Domínguez-Vías, Germán; Durán, Raquel; Vives, Francisco
Previous studies demonstrated an asymmetry of left predominance for mean values of soluble leucine aminopeptidase (LeuAP) activity in the frontal cortex (FC) and hypothalamus of adult male rats, fluorimetrically analyzed by the hydrolysis of Leu-β-naphthylamide as a substrate. No asymmetries were observed in nine other left (L) and right (R) regions obtained from rostro-caudally sectioned coronal slices. Neither had inter-hemispheric differences observed for lactate dehydrogenase (LDH), analyzed simultaneously in the same brain regions (L and R) of the same animals. However, the level of intra-hemispheric or inter-hemispheric correlation of LeuAP or LDH between such brain regions has not been analyzed. In order to obtain additional suggestions on the functional heterogeneity between regions of LeuAP and LDH, in the present investigation, the level of intra-hemispheric and inter-hemispheric correlations of the frontal cortex with the rest of the regions studied is described: (A) between the left frontal cortex (LFC) and the rest of the left regions; (B) between the right frontal cortex (RFC) and the rest of the right regions; (C) between the left frontal cortex and all of the right regions; and (D) between the right frontal cortex and all of the left regions. All of the correlations obtained were positive. The intra-hemispheric analysis showed a greater heterogeneity of values in the correlations observed between RFC and the rest of the right regions than between LFC and the rest of the left regions. Greater heterogeneity is observed when comparing RFC correlations with left regions than when comparing LFC correlations with right regions. In conclusion, the greatest heterogeneity (suggesting a greater functional variability) was observed in the right intra-hemispheric analysis and in the inter-hemispheric analysis between the RFC and the left hemisphere. The results for LDH showed a great homogeneity between regions both in the intra- and inter-hemispheric studies.
Asymmetrical effect of captopril on the angiotensinase activity in frontal cortex and plasma of the spontaneously hypertensive rats: expanding the model of neuroendocrine integration.
(Elsevier, 2012-03-01) Segarra, Ana Belén; Prieto-Gómez, María Isabel; Banegas, Inmaculada; Villarejo, Ana Belén; Wangensteen, Rosemary; de-Gasparo, Marc; Vives, Francisco; Ramírez-Sánchez, Manuel
There is a reciprocal connection between the frontal cortex (FC) and cardiovascular function, and this connection is functionally lateralized. The possible pathophysiological impact of neuroendocrine asymmetries is largely underestimated. Our aim was to examine the activity of soluble (SOL) and membrane-bound (MB) aminopeptidases (APs) involved in the renin-angiotensin system in the peripheral plasma and in the left and right FC, in both untreated (control) and captopril-treated spontaneously hypertensive rats (SHRs). Enzymatic activities were measured fluorometrically using arylamide derivatives as substrates. Captopril reduced systolic blood pressure, but no differences in plasma AP activity were observed between the control and treated SHRs. In contrast, whereas the bilateral pattern (left vs. right differences) of SOL activities did not substantially change in the FC after captopril treatment, the asymmetries observed for MB activities in the FC markedly increased compared with the control group. Moreover, correlations between the AP activities in the plasma and those in the left or right FC were observed. In the control rats, the plasma AP activities correlated significantly with those in the right FC, whereas they correlated with those in the left FC in the captopril-treated group. In both groups (control and captopril), these correlations were negative for the SOL activity but positive for the MB activity. The present results reveal a pattern of bilateral behavior between the nervous and cardiovascular systems. The inverted bilateral behavior after captopril treatment suggests a systematized, lateralized neuroendocrine response representing a regular bilateral behavior that has yet to be analyzed.
Bilateral Correlational Behavior of Pyroglutamate Aminopeptidase I Activity in Rat Photoneuroendocrine Locations During a Standard 12:12 h Light-Dark Cycle
(MDPI, 2024-11) Ramírez-Sánchez, Manuel; Prieto-Gómez, María Isabel; Segarra, Ana Belén; Banegas, Inmaculada; Martínez-Cañamero, Magdalena; Domínguez-Vías, Germán; Durán, Raquel; Vives, Francisco
We previously described the circadian variation and bilateral distribution of pyroglutamate aminopeptidase I (pGluPI) activity levels in photoneuroendocrine locations of adult male rats during a standard 12:12 h light-dark cycle. However, the correlational analysis between such locations has not yet been studied. This may provide new data about the unilateral and bilateral functional interaction between photoneuroendocrine locations under light and dark conditions. We analyzed the correlations between locations of a photoneuroendocrine circuit consisting of retina, anterior hypothalamus, superior cervical ganglion, and pineal gland, as well as other related photoneuroendocrine locations: posterior hypothalamus, anterior pituitary, posterior pituitary, occipital cortex, and serum. In particular, we analyzed the correlations between the left retina or the right retina versus the rest of the locations, as well as the correlations between the left and right sides of paired structures at the different time points selected from 12 h light and 12 h dark periods. Also, the profiles of correlational results were compared with the corresponding mean levels. The results demonstrate the complexity of asymmetrical brain behavior. The correlation profile did not always parallel the profile observed with the mean activity values. The diurnal behavior of correlations with the left or right retina differed from one location to another. Likewise, the diurnal variation of correlations between the left and right sides of the paired structures differed between them. Particularly, while most correlations between the left versus right sides of paired structures showed positive values, that of the posterior hypothalamus showed a negative value at 13 h of light period. In addition, except the posterior hypothalamus, most paired locations only correlated significantly with right retina at 07 h of the light period. The results demonstrate the dynamic complexity of brain asymmetry, which represents a challenge for understanding its functional meaning.
Blood Pressure Correlates Asymmetrically with Neuropeptidase Activities of the Left and Right Frontal Cortices
(MDPI, 2021-01) Segarra, Ana Belén; Prieto-Gómez, María Isabel; Banegas, Inmaculada; Martínez-Cañamero, Magdalena; de-Gasparo, Marc; Ramírez-Sánchez, Manuel
A lateralized distribution of neuropeptidase activities in the frontal cortex of normotensive and hypertensive rats has been described depending on the use of some vasoactive drugs and linked to certain mood disorders. Asymmetrical neuroperipheral connections involving neuropeptidases from the left or right hemisphere and aminopeptidases from the heart or plasma have been suggested to play a role in this asymmetry. We hypothesize that such asymmetries could be extended to the connection between the brain and physiologic parameters and metabolic factors from plasma and urine. To assess this hypothesis, we analyzed the possible correlation between neuropeptidases from the left and right frontal cortex with peripheral parameters in normotensive (Wistar Kyoto [WKY]) rats and hypertensive rats (spontaneously hypertensive rats [SHR]) untreated or treated with vasoactive drugs such as captopril, propranolol and L-nitro-arginine methyl ester. Neuropeptidase activities from the frontal cortex were analyzed fluorometrically using arylamide derivatives as substrates. Physiological parameters and metabolic factors from plasma and urine were determined using routine laboratory techniques. Vasoactive drug treatments differentially modified the asymmetrical neuroperipheral pattern by changing the predominance of the correlations between peripheral parameters and central neuropeptidase activities of the left and right frontal cortex. The response pattern also differed between SHR and WKY rats. These results support an asymmetric integrative function of the organism and suggest the possibility of a different neurometabolic response coupled to particular mood disorders, depending on the selected vasoactive drug.
Brain, Heart and Kidney Correlate for the Control of Blood Pressure and Water Balance: Role of Angiotensinases.
(Karger, 2014-10) Prieto-Gómez, María Isabel; Villarejo, Ana Belén; Segarra, Ana Belén; Banegas, Inmaculada; Wangensteen, Rosemary; Martínez-Cañamero, Magdalena; de-Gasparo, Marc; Vives, Francisco; Ramírez-Sánchez, Manuel
The renin-angiotensin system (RAS) plays a major role in the control of blood pressure (BP) and water balance by coordinating brain, heart and kidney functions, connected with each other by hormonal and neural mechanisms through the autonomic nervous system (ANS). RAS function may be monitored by the study of the enzymes (angiotensinases) involved in the metabolism of its active peptides. In order to study the relationship between the brain-heart-kidney axis and the control of BP and water balance, we analyzed the correlation of angiotensinase activities, assayed as arylamidase activities, between hypothalamus, left ventricle, renal cortex and renal medulla, collected from Wistar-Kyoto and spontaneously hypertensive rats, treated or not treated with L-NAME [N(G)-nitro-L-arginine methyl ester]. This compound not only inhibits the formation of nitric oxide but also disrupts the normal function of the ANS activating the sympathetic nervous system (SNS) to increase BP. In addition, to assess the influence of the SNS, we studied the effect of its blockade by treatment of both strains with propranolol. The present results support the notion that RAS function of the brain-heart-kidney axis, as reflected by the activities of angiotensinases, is reciprocally connected by afferent and efferent mechanisms between these locations, presumably through the ANS. These results reveal new aspects of neuroendocrine regulation possibly involving the ANS.
Correlational Study of Aminopeptidase Activities between Left or Right Frontal Cortex versus the Hypothalamus, Pituitary, Adrenal Axis of Spontaneously Hypertensive Rats Treated with Hypotensive or Hypertensive Agents.
(MDPI, 2023-11-06) Prieto-Gómez, María Isabel; Segarra, Ana Belén; Banegas, Inmaculada; Martínez-Cañamero, Magdalena; Durán, Raquel; Vives, Francisco; Domínguez-Vías, Germán; Ramírez-Sánchez, Manuel
It has been suggested that the neuro-visceral integration works asymmetrically and that this asymmetry is dynamic and modifiable by physio-pathological influences. Aminopeptidases of the renin-angiotensin system (angiotensinases) have been shown to be modifiable under such conditions. This article analyzes the interactions of these angiotensinases between the left or right frontal cortex (FC) and the same enzymes in the hypothalamus (HT), pituitary (PT), adrenal (AD) axis (HPA) in control spontaneously hypertensive rats (SHR), in SHR treated with a hypotensive agent in the form of captopril (an angiotensin-converting enzyme inhibitor), and in SHR treated with a hypertensive agent in the form of the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). In the control SHR, there were significant negative correlations between the right FC with HPA and positive correlations between the left FC and HPA. In the captopril group, the predominance of negative correlations between the right FC and HPA and positive correlations between the HPA and left FC was maintained. In the L-NAME group, a radical change in all types of interactions was observed; particularly, there was an inversion in the predominance of negative correlations between the HPA and left FC. These results indicated a better balance of neuro-visceral interactions after captopril treatment and an increase in these interactions in the hypertensive animals, especially in those treated with L-NAME.
Functional and neurometabolic asymmetry in SHR and WKY rats following vasoactive treatments
(Nature Portfolio, 2019-12-01) Segarra, Ana Belén; Prieto-Gómez, María Isabel; Banegas, Inmaculada; Martínez-Cañamero, Magdalena; Luna, Juan Dios; de-Gasparo, Marc; Ramírez-Sánchez, Manuel
A lateralized distribution of neuropeptidase activities in the frontal cortex of normotensive and hypertensive rats has been described depending on the use of some vasoactive drugs and linked to certain mood disorders. Asymmetrical neuroperipheral connections involving neuropeptidases from the left or right hemisphere and aminopeptidases from the heart or plasma have been suggested to play a role in this asymmetry. We hypothesize that such asymmetries could be extended to the connection between the brain and physiologic parameters and metabolic factors from plasma and urine. To assess this hypothesis, we analyzed the possible correlation between neuropeptidases from the left and right frontal cortex with peripheral parameters in normotensive (Wistar Kyoto [WKY]) rats and hypertensive rats (spontaneously hypertensive rats [SHR]) untreated or treated with vasoactive drugs such as captopril, propranolol and L-nitro-arginine methyl ester. Neuropeptidase activities from the frontal cortex were analyzed fluorometrically using arylamide derivatives as substrates. Physiological parameters and metabolic factors from plasma and urine were determined using routine laboratory techniques. Vasoactive drug treatments differentially modified the asymmetrical neuroperipheral pattern by changing the predominance of the correlations between peripheral parameters and central neuropeptidase activities of the left and right frontal cortex. The response pattern also differed between SHR and WKY rats. These results support an asymmetric integrative function of the organism and suggest the possibility of a different neurometabolic response coupled to particular mood disorders, depending on the selected vasoactive drug. © 2019, The Author(s).
Interaction between Angiotensinase Activities in Pituitary and Adrenal Glands of Wistar–Kyoto and Spontaneously Hypertensive Rats under Hypotensive or Hypertensive Treatments
(MDPI, 2021-07-22) Segarra, Ana Belén; Prieto-Gómez, María Isabel; Banegas, Inmaculada; Martínez-Cañamero, Magdalena; Villarejo, Ana Belén; Domínguez-Vías, Germán; de-Gasparo, Marc; Ramírez-Sánchez, Manuel
In the present study, we analyzed the activity of several aminopeptidases (angiotensinases) involved in the metabolism of various angiotensin peptides, in pituitary and adrenal glands of untreated Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) or treated with the antihypertensive drugs captopril and propranolol or with the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). Intra- and inter-gland correlations between angiotensinase activities were also calculated. Membrane-bound alanyl-, cystinyl-, and glutamyl-aminopeptidase activities were determined fluorometrically using aminoacyl-β-naphthylamide as substrates. Depending on the type of angiotensinase analyzed, the results reflect a complex picture showing substantial differences between glands, strains, and treatments. Alanyl-aminopeptidase responsible for the metabolism of Ang III to Ang IV appears to be the most active angiotensinase in both pituitary and adrenals of WKY and particularly in SHR. Independently of treatment, most positive correlations are observed in the pituitary gland of WKY whereas such positive correlations are predominant in adrenals of SHR. Negative inter-gland correlations were observed in control SHR and L-NAME treated WKY. Positive inter-gland correlations were observed in captopril-treated SHR and propranolol-treated WKY. These results may reflect additional mechanisms for increasing or decreasing systolic blood pressure in WKY or SHR.
Stress influences brain enkephalinase, oxytocinase and angiotensinase activities: a new hypothesis.
(Karger, 2009-05-20) Hernández, Joaquín; Segarra, Ana Belén; Ramírez-Sánchez, Manuel; Banegas, Inmaculada; de-Gasparo, Marc; Alba, Francisco; Vives, Francisco; Durán, Raquel; Prieto-Gómez, María Isabel
Brain enkephalin and oxytocin are anxiolytic agents involved in the response mechanism to stress. Degrading enzymes such as enkephalinase and oxytocinase could also be associated with this response. The effect of acute immobilization stress on enkephalinase and oxytocinase activities was determined in the soluble and membrane fractions of the medial prefrontal cortex, hippocampus and amygdala using alanyl- and leucyl-beta-naphthylamide as substrates, the latter in the presence and absence of 20 mM L-methionine. No change in aminopeptidase activities was observed in the prefrontal cortex of stressed rats. In contrast, enkephalinase activity decreased in the soluble fraction of the hippocampus but increased in the membrane fraction. In the amygdala, soluble oxytocinase and membrane enkephalinase activities decreased in stressed animals. These results show that acute immobilization stress affects differentially enkephalinase and oxytocinase activities depending on the fraction and brain region analyzed. A reduction in the activity of soluble enkephalinase in the hippocampus and soluble oxytocinase as well as membrane enkephalinase in the amygdala may suggest higher availability/longer action of enkephalin and oxytocin at these locations. This may explain the relative importance of these enzymatic activities in the anxiolytic properties proposed for enkephalins and oxytocin in the hippocampus and amygdala during stress conditions. This interpretation is not applicable to membrane enkephalinase activity in the hippocampus. However, alanyl-beta-naphthylamide hydrolyzing activity not only measures enkephalinase activity, it also reflects the angiotensinase-induced metabolism of angiotensin III to angiotensin IV. Therefore, our results may also mirror an increase in the formation of Ang IV in hippocampus and a decrease in the amygdala in acute stress. In conclusion, aminopeptidase activities in the hippocampus and amygdala may affect enkephalin, oxytocin and angiotensin III metabolism during acute immobilization stress and therefore be involved in the anxiolytic response.
The renin-angiotensin system: new insight into old therapies.
(BENTHAM SCIENCE PUBL LTD, 2013-04) Ramírez-Sánchez, Manuel; Prieto-Gómez, María Isabel; Wangensteen, Rosemary; Banegas, Inmaculada; Segarra, Ana Belén; Villarejo, Ana Belén; Vives, Francisco; Cobo-Domingo, Justo; de-Gasparo, Marc
Although the renin-angiotensin system (RAS) is already an old acquaintance, there are often exciting discoveries that improve our knowledge of it and open new therapeutic possibilities. Moreover, well-established drugs, such as angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), or beta-blockers, show that their mechanism of action may be the result of parallel pathways other than the ones initially established. A detailed analysis of the RAS can be carried out in part through the study of the enzymes, named angiotensinases, involved in its cascade, whose activity is a reflection of the functionality of their peptide substrates. The study of these enzymes offers the possibility of controlling the effects of angiotensins through various pharmacological manipulations. For example, angiotensinase inhibitors or activators are being used or have been proposed as antihypertensive agents. They have also been suggested as analgesic and antidepressant drugs or targets for drug development against different pathologies such as Alzheimer's disease, epilepsy or ischemia. On the other hand, the analysis of brain asymmetry has revealed surprising results about the laterality of central and peripheral components of the RAS. Such studies indicate that the neurovisceral integration, already proposed by Claude Bernard (1867) should also be analyzed from a bilateral perspective. In this review, the RAS and the role of various angiotensinases implicated in the cascade are revisited. Therapeutic strategies involving some components of the RAS with an unusual vision resulting from a bilateral perspective added to their study are discussed.
Vasoconstrictor and Pressor Effects of Des-Aspartate-Angiotensin I in Rat
(MDPI, 2022-05-25) Wangensteen, Rosemary; Gómez-Guzmán, Manuel; Banegas, Inmaculada; Rodríguez-Gómez, Isabel; Jiménez-Moleón, Rosario; Duarte, Juan; García-Estaño, Joaquín; Vargas, Félix
This study investigated the vasoactive effects of des-aspartate-angiotensin-I (DAA-I) in male Wistar rats on whole body vascular bed, isolated perfused kidneys, and aortic rings. Dose–response curves to DAA-I were compared with those to angiotensin II (Ang II). The Ang II-type-1 (AT1) receptor blocker, losartan, was used to evaluate the role of AT1 receptors in the responses to DAA-I. Studies were also conducted of the responsiveness in aortic rings after endothelium removal, nitric oxide synthase inhibition, or AT2 receptor blockade. DAA-I induced a dose-related systemic pressor response that was shifted to the right compared with Ang II. Losartan markedly attenuated the responsiveness to DAA-I. DAA-I showed a similar pattern in renal vasculature and aortic rings. In aortic rings, removal of endothelium and nitric oxide inhibition increased the sensitivity and maximal response to DAA-I and Ang II. AT2 receptor blockade did not significantly affect the responsiveness to DAA-I. According to these findings, DAA-I increases the systemic blood pressure and vascular tone in conductance and resistance vessels via AT1 receptor activation. This vasoconstrictor effect of DAA-I participates in the homeostatic control of arterial pressure, which can also contribute to the pathogenesis of hypertension. DAA-I may therefore be a potential therapeutic target in cardiovascular disease.

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Examinando por Autor "Banegas, Inmaculada"