Regulation Of Systemic Blood Pressure Research Articles

Seizure-related modulation of systemic arterial blood pressure in focal epilepsy.

Cardiorespiratory function alterations are commonly observed with epileptic seizures and may lead to syncope and sudden unexpected death in epilepsy (SUDEP). Although most previous research has focused on controlling heart rate (HR) and respiration, little is known about seizure-related regulation of systemic blood pressure (BP). Herein, we have investigated whether the periictal modulation of systemic BP and HR depends on seizure characteristics. Systemic arterial BP, HR, and peripheral capillary oxygen saturation (SPO2 ) were continuously and noninvasively monitored using the ccNexfin device in those epilepsy patients undergoing video-electroencephalography (EEG) telemetry. Data are given as mean ± standard deviation (SD). Forty-five seizures in 37 patients were included. In focal seizures (FS, n = 35), the mean arterial BP (MAP) increased by 33 ± 35% and the HR by 53 ± 44%, whereas the SPO2 remained unaltered. The MAP and HR increases were significantly greater in FS with alterations in consciousness than in those without. For those FS that evolved to bilateral convulsive seizures (BCS, n = 10), all of the ictal recordings were compromised by artifacts. However, 2 min after seizure cessation, the MAP was enhanced by only 16 ± 14% and returned to a baseline slightly below preictal levels after 5 min, whereas the HR was increased by 77 ± 33% and remained elevated throughout the postictal phase. Periictal regulation of systemic BP and HR displays distinct patterns depending on the type of seizure with focal onset. These changes were unrelated to alterations in SPO2 . The potential clinical implications of these findings are discussed in the article.

Microinjection of acetylcholine into cerebellar fastigial nucleus induces blood depressor response in anesthetized rats

It is well known that the cerebellar fastigial nucleus (FN) is involved in cardiovascular modulation, and has direct evidence of cholinergic activity; however, whether and how acetylcholine (ACh) in the FN modulates blood pressure has not been investigated. In this study, we analyzed mean arterial pressure, maximal change in mean arterial pressure, and the reaction time of blood pressure changes after microinjection of cholinergic reagents into the FN in anesthetized rats. The results showed that ACh evoked a concentration-dependent (10, 30 and 100mM) effect on blood pressure down-regulation. The muscarinic ACh (mACh) receptor antagonist atropine, but not the nicotinic ACh (nACh) receptor antagonist mecamylamine, blocked the ACh-mediated depressor response. The mACh receptor agonist oxotremorine M, rather than nACh receptor agonist nicotine, mimicked the ACh-mediated blood pressure decrease in a dose-dependent manner (10, 30 and 100mM). These results indicate that cholinergic input in the cerebellar FN exerts a depressor effect on systemic blood pressure regulation, and such effects are substantially contributed by mACh rather than nACh receptors, although the precise mechanism concerning the role of mACh receptor in FN-mediated blood pressure modulation remains to be elucidated.

Noise enhanced the electrical stimulation-contractile response coupling in isolated mouse heart

BackgroundStochastic resonance is a phenomenon that allows a system to improve its capability to detect stimulus when a limited amount of noise is added to the stimuli. It has experimentally been shown that noise enhances the homeostatic function of the blood pressure regulatory system. This study aimed to investigate whether the noise can enhance the contractile response in the whole heart. MethodsExperiments were conducted in isolated mouse hearts (0.040kg, n=8), a Langendorff heart preparation is used to obtain two variables of the contractile response contraction force and heart rate. The contractile response due to an electrical stimulation perturbed with Gaussian noise was recorded. ResultsThe results show that the intensity of noise induced in the electrical stimuli has an effect on the electrical stimulation-contractile response coupling. With 10% noise induced, the bandwidth where the synchronization effect is presented was increased from (7–11Hz) to (6–12Hz), and the irregular dynamic threshold was changed to 13Hz. ConclusionsWe find that the noise increases the synchronization bandwidth in the electrical stimulation-contractile response coupling. We have experimentally demonstrated the stochastic resonance in isolated mouse heart.

Abstract MP01: Vascular versus Tubular Renin: Role in Kidney Development

Renin, the key regulated enzyme of the renin angiotensin system regulates blood pressure and fluid electrolyte homeostasis as well as morphogenesis of the kidney. Classically, renin is synthesized and released from juxtaglomerular cells located in the afferent arterioles at the entrance to the glomeruli. It has also been suggested that renin may also be synthesized by tubular cells. Interestingly, whole body deletion of the renin gene results in striking vascular and tubular abnormalities, hydronephrosis and a urine-concentrating defect. Given the complexity of such phenotype, it has not been possible to discriminate the relative contributions of vascular versus tubular renin. To investigate the relative contribution of renin in the vascular versus tubular compartments during kidney development we deleted renin independently in either compartment by crossing Ren1cfl/fl mice to Foxd1-cre or to Hoxb7-cre mice. We performed blood chemistries, histological analysis, immunostaining for specific cell markers, total kidney renin mRNA quantification and ELISA for renin in plasma. Vascular deletion of renin (Foxd1 lineage) resulted in neonatal mortality that could be rescued with daily injections of saline suggesting that this phenotype is due to an inability to concentrate the urine and improper medullary development. These mice showed absence of renal renin and negligible levels of plasma renin. Histologically, the kidneys had abnormal development of its arterioles, which became progressively thickened by disorganized, concentric hypertrophy of smooth muscle cells and marked hydronephrosis. On the other hand, lack of renin in the collecting ducts (Hoxb7 descendants) did not affect kidney morphology, intra-renal renin distribution, kidney renin mRNA expression or circulating renin during basal conditions or in response to a homeostatic stress such as low sodium diet. We conclude that renin generated in the renal vascular compartment is fundamental for the development and integrity of the kidney whereas the presence of renin in the collecting duct system is dispensable for normal kidney development and cannot compensate for the lack of renin in the vascular compartment. Further, the main source of circulating renin is the kidney vasculature.

Vascular versus tubular renin: role in kidney development.

Renin, the key regulated enzyme of the renin-angiotensin system regulates blood pressure, fluid-electrolyte homeostasis, and renal morphogenesis. Whole body deletion of the renin gene results in severe morphological and functional derangements, including thickening of renal arterioles, hydronephrosis, and inability to concentrate the urine. Because renin is found in vascular and tubular cells, it has been impossible to discern the relative contribution of tubular versus vascular renin to such a complex phenotype. Therefore, we deleted renin independently in the vascular and tubular compartments by crossing Ren1(c fl/fl) mice to Foxd1-cre and Hoxb7-cre mice, respectively. Deletion of renin in the vasculature resulted in neonatal mortality that could be rescued with daily injections of saline. The kidneys of surviving mice showed the absence of renin, hypertrophic arteries, hydronephrosis, and negligible levels of plasma renin. In contrast, lack of renin in the collecting ducts did not affect kidney morphology, intra-renal renin, or circulating renin in basal conditions or in response to a homeostatic stress, such as sodium depletion. We conclude that renin generated in the renal vasculature is fundamental for the development and integrity of the kidney, whereas renin in the collecting ducts is dispensable for normal kidney development and cannot compensate for the lack of renin in the vascular compartment. Further, the main source of circulating renin is the kidney vasculature.

Role of cerebellar adrenomedullin in blood pressure regulation

Adrenomedullin (AM) and their receptor components, calcitonin-receptor-like receptor (CRLR) and receptor activity-modifying protein (RAMP1, RMP2 and RAMP3) are widely expressed in the central nervous system, including cerebellum. We have shown that AM binding sites are altered in cerebellum during hypertension, suggesting a role for cerebellar adrenomedullinergic system in blood pressure regulation. To further evaluate the role of AM in cerebellum, we assessed the expression of AM, RAMP1, RAMP2, RAMP3 and CRLR in the cerebellar vermis of 8 and 16week old spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. In addition, the effect of microinjection of AM into rat cerebellar vermis on arterial blood pressure (BP) was determined. Animals were sacrificed by decapitation and cerebellar vermis was dissected for quantification of AM, CRLR, RAMP1, RAMP2 and RAMP3 expression using western blot analysis. Another group of male, 16week old SHR and WKY rats was anesthetized, and a cannula was implanted in the cerebellar vermis. Following recovery AM (0.02 to 200pmol/5μL) or vehicle was injected into cerebellar vermis. BP was determined, before and after treatments, by non-invasive plethysmography. In addition, to establish the receptor subtype involved in AM action in vivo, animals received microinjections of AM22–52 (200pmol/5μL), an AM1 receptor antagonist, or the CGRP1 receptor antagonist, CGRP8–37 (200pmol/5μL) into the cerebellar vermis, administered simultaneously with AM or vehicle microinjection. Cannulation was verified post mortem with the in situ injection of a dye solution. Our findings demonstrated that the expression of CRLR, RAMP1 and RAMP3 was higher in cerebellum of SHR rats, while AM and RAMP2 expression was lower than those of WKY rats, both in 8 and 16week old rats. In vivo microinjection of AM into the cerebellar vermis caused a profound, dose dependent, hypotensive effect in SHR but not in normotensive WKY rats. Coinjections of a putative AM receptor antagonist, AM22–52 abolished the decreases in mean arterial pressure (MAP) evoked by AM, showing that AM acts through its AM1 receptor in the vermis to reduce MAP. These findings demonstrate a dysregulation of cerebellar AM-system during hypertension, and suggest that cerebellar AM plays an important role in the regulation of BP. Likewise; they constitute a novel mechanism of BP control which has not been described so far.

Angiotensin type 1a receptor deficiency decreases amyloid β-protein generation and ameliorates brain amyloid pathology.

Alzheimer’s disease is characterized by neuronal loss and cerebral accumulation of amyloid-β protein (Aβ) and lowering the generation of Aβ is a pivotal approach in the strategy of Alzheimer’s disease treatment. Midlife hypertension is a major risk factor for the future onset of sporadic Alzheimer’s disease and the use of some antihypertensive drugs may decrease the incidence of Alzheimer’s disease. However, it is largely unknown how the blood pressure regulation system is associated with the pathogenesis of Alzheimer’s disease. Here we found that the deficiency of angiotensin type 1a receptor (AT1a), a key receptor for regulating blood pressure, significantly decreased Aβ generation and amyloid plaque formation in a mouse model of Alzheimer’s disease. The lack of AT1a inhibited the endocleavage of presenilin-1 (PS1), which is essential for γ-secretase complex formation and Aβ generation. Notably, the ligand of AT1a, angiotensin II, enhanced Aβ generation, PS1 endocleavage and γ-secretase complex formation. Our results suggest that AT1a activation is closely associated with Aβ generation and brain amyloid accumulation by regulating γ-secretase complex formation. Thus, removal of life style factors or stresses that stimulate AT1a to elevate blood pressure may decrease Aβ generation and brain amyloid accumulation, thereby preventing the pathogenesis of Alzheimer’s disease.

The identification and neurochemical characterization of central neurons that target parasympathetic preganglionic neurons involved in the regulation of choroidal blood flow in the rat eye using pseudorabies virus, immunolabeling and conventional pathway tracing methods.

The choroidal blood vessels of the eye provide the main vascular support to the outer retina. These blood vessels are under parasympathetic vasodilatory control via input from the pterygopalatine ganglion (PPG), which in turn receives its preganglionic input from the superior salivatory nucleus (SSN) of the hindbrain. The present study characterized the central neurons projecting to the SSN neurons innervating choroidal PPG neurons, using pathway tracing and immunolabeling. In the initial set of studies, minute injections of the Bartha strain of the retrograde transneuronal tracer pseudorabies virus (PRV) were made into choroid in rats in which the superior cervical ganglia had been excised (to prevent labeling of sympathetic circuitry). Diverse neuronal populations beyond the choroidal part of ipsilateral SSN showed transneuronal labeling, which notably included the parvocellular part of the paraventricular nucleus of the hypothalamus (PVN), the periaqueductal gray, the raphe magnus (RaM), the B3 region of the pons, A5, the nucleus of the solitary tract (NTS), the rostral ventrolateral medulla (RVLM), and the intermediate reticular nucleus of the medulla. The PRV+ neurons were located in the parts of these cell groups that are responsive to systemic blood pressure signals and involved in systemic blood pressure regulation by the sympathetic nervous system. In a second set of studies using PRV labeling, conventional pathway tracing, and immunolabeling, we found that PVN neurons projecting to SSN tended to be oxytocinergic and glutamatergic, RaM neurons projecting to SSN were serotonergic, and NTS neurons projecting to SSN were glutamatergic. Our results suggest that blood pressure and volume signals that drive sympathetic constriction of the systemic vasculature may also drive parasympathetic vasodilation of the choroidal vasculature, and may thereby contribute to choroidal baroregulation during low blood pressure.

The role of genetic factors in the pathogenesis of neonatal intraventricular hemorrhage

Intraventricular hemorrhage (IVH) affects 15-20% of babies born before 32 weeks of pregnancy. Besides gestational age (below 32 weeks) there are a number of IVH risk factors. Increasing attention is being paid to genetic factors in the development of IVH. The authors discuss genetic factors (mutations of coagulation factors, gene polymorphisms in pro-inflammatory cytokines, mutation of type IV collagen gene, polymorphisms of genes responsible for the regulation of systemic blood pressure and cerebral blood flows) whose involvement in IVH pathogenesis has been confirmed in the highest number of reports and for which being a carrier plays an important role in their pathophysiology. The role of genetic factors in IVH remains unclear. Further analysis of the role of genetic factors in the pathophysiology of IVH will make it possible to determine the group of newborns who are specifically at risk of developing IVH in the perinatal period.

Counter-regulatory effects played by the ACE - Ang II - AT1 and ACE2 - Ang-(1-7) - Mas axes on the reactive oxygen species-mediated control of vascular function: perspectives to pharmacological approaches in controlling vascular complications.

The Renin-Angiotensin system plays an important role in the regulation of systemic blood pressure as well as in fluid and electrolyte balance. It is divided into two described axes, the ACE - Ang II - AT1 receptor, with Ang II as the main mediator, and the ACE2 - Ang-(1-7) - Mas receptor, with Ang-(1-7) responsible for the main effects. The main vascular effect induced by Ang II is contraction, while Ang-(1-7) includes relaxation in several vascular beds. Ang II also activates several cytokines that are important in the genesis of vascular inflammation and hypertrophy. In this context, Ang-(1-7) seems to have a protective role. Both AT1 and Mas receptors modulate, in different ways, the generation of, which are involved in the control of vascular tone and the genesis of vascular dysfunction triggered by several diseases, including diabetes mellitus, arterial hypertension and atherosclerosis. Thereby, this review presents an overview of the modulation played by the whole Renin-Angiotensin system on the reactive oxygen species-mediated control of vascular tone and the oxidative stress-elicited vascular dysfunction.

Is There a Role for the Incretin System in Blood Pressure Regulation?

Incretin-based therapies are now well established for diabetes management and are among the frontline agents for control of hyperglycemia. In addition to their antihyperglycemic effects, evidence is emerging on the role of these agents on blood pressure regulation, cardioprotective and renoprotective properties. Because of the pleiotropic nature of these affects, these agents could offer significant benefits with regards to the cardiorenal metabolic complications that are part of the diabetes and obesity epidemic in the United States and worldwide. We review the various known mechanisms or pathways by which incretin based therapy exerts its regulation of blood pressure with emphasis on novel mechanisms such as inflammation/immunomodulation and oxidative stress.

Modeling of the Blood Pressure Regulation System in Rats Using Genetic Algorithms

Abstract Blood pressure (BP) is one of the principal vital signs. The regulation of normal BP is critical for maintaining the normal functioning of an organism. The structure of the BP regulation in vertebrates, including humans, is very complex and it is not yet fully understood. There are several BP regulation subsystems which interact together. In this study, we analysed and modelled the role of the most important BP regulation systems (sympathetic nervous system, renin-angiotensin-aldosterone system, L-Arginine/nitric oxide) as well as the role of reactive oxygen species, the imbalance of which is implied in the development of hypertension disease. Our aim is to design a dynamic model of the BP regulation in normotensive rats, which can help us better understand the complex process of BP regulation. The BP responses were measured in conscious rats after acute stress with or without the application of selected drugs, which can inhibit particular regulation subsystems. Linear dynamic models of particular regulation subsystems were identified using genetic algorithms. Each subsystem is a feedback loop, which contains both the system dynamics and the controller. We describe the simulation-based identification procedure of these particular models as well as of the entire BP regulation system.

Asociación y efectos de interacción en los genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2 sobre la hipertensión en población antioqueña

Hypertension is a multifactorial disease influenced by genetic and environmental components, with its prevalence varying across ethnic groups. Manifold studies on blood pressure regulatory system genes have been carried out -such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, endothelial factor, and sodium balance-, but the results yielded were inconsistent among populations. To evaluate the effect of both variants in genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R PTGS2, and the result of the individual ancestry component on hypertension and blood pressure levels among population in Antioquia. 107 cases and 253 controls were genotyped for 12 variants on genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2, and for 20 ancestry informative markers. The association of polymorphisms and their interactions, and the association of ancestral genetic composition with hypertension and blood pressure levels were examined. Genes ADD2, rs4852706 (OR=3.0; p=0.023); DRD1, rs686 (OR=0.38; p=0.012) and ADRB2, rs1042718 (OR=10.0; p=0.008); as well as genotypic combinations of DRD1 and AGTR1; AGT and ADD1; and ADD1 to ATP2B1 and PTGS2 were associated to hypertension. The Amerindian ancestry component was associated to some decrease in diastolic blood pressure. Variants on genes ADD2, DRD1, ADRB2, AGTR1, AGT, ADD1, ATP2B1 and PTGS2 individually or interacting, are associated to hypertension. The Amerindian ancestry component has an effect on blood pressure.

自然発症高血圧ラットにおける内因性ジギタリス様物質, マリノブフォトキシンの動態 —血圧調節におけるレニン·アンジオテンシン系の関与について

自然発症高血圧ラットにおける内因性ジギタリス様物質, マリノブフォトキシンの動態 —血圧調節におけるレニン·アンジオテンシン系の関与について

Circulating Blood Endothelial Nitric Oxide Synthase Contributes to the Regulation of Systemic Blood Pressure and Nitrite Homeostasis

Mice genetically deficient in endothelial nitric oxide synthase (eNOS(-/-)) are hypertensive with lower circulating nitrite levels, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. Although the current paradigm holds that this bioactivity derives specifically from the expression of eNOS in endothelium, circulating blood cells also express eNOS protein. A functional red cell eNOS that modulates vascular NO• signaling has been proposed. To test the hypothesis that blood cells contribute to mammalian blood pressure regulation via eNOS-dependent NO• generation, we cross-transplanted wild-type and eNOS(-/-) mice, producing chimeras competent or deficient for eNOS expression in circulating blood cells. Surprisingly, we observed a significant contribution of both endothelial and circulating blood cell eNOS to blood pressure and systemic nitrite levels, the latter being a major component of the circulating NO• reservoir. These effects were abolished by the NOS inhibitor L-NG-nitroarginine methyl ester and repristinated by the NOS substrate L-arginine and were independent of platelet or leukocyte depletion. Mouse erythrocytes were also found to carry an eNOS protein and convert (14)C-arginine into (14)C-citrulline in NOS-dependent fashion. These are the first studies to definitively establish a role for a blood-borne eNOS, using cross-transplant chimera models, that contributes to the regulation of blood pressure and nitrite homeostasis. This work provides evidence suggesting that erythrocyte eNOS may mediate this effect.

Nociceptin receptor signaling in sympathetic neurons from septic rats

BackgroundThe endogenous opioid peptide, nociception (Noc), contributes to the regulation of systemic blood pressure and regional blood flow. Recent clinical and animal studies have reported that Noc and its receptor (nociceptin/orphanin FQ [NOP]) are involved in inflammation and sepsis. The purpose of the present study was to examine the modulation of Ca2+ channels by Noc in acutely isolated stellate ganglion (SG) neurons from control and septic rats. Materials and methodsSepsis was induced in male Sprague–Dawley rats via cecal ligation and puncture. SG neurons were isolated 24 and 72 h after sepsis induction. Thereafter, the concentration–response relationships for the Noc-stimulated NOP receptor Ca2+ current inhibition were determined using the whole-cell patch clamp technique. In addition, the Noc precursor (prepronociceptin [PNOC]) and NOP receptor messenger RNA (mRNA) levels were determined by quantitative real-time polymerase chain reaction, and PNOC protein levels were measured by Western blot analysis. ResultsComparison of the Noc concentration–response relationships in SG neurons from control and septic rats 24 h after sepsis revealed similar potency and efficacy. Moreover, 72 h after sepsis, neurons from control and septic rats exhibited an increased potency compared with both groups at the 24-h time point—an effect that was more pronounced in neurons from septic rats. PNOC mRNA levels were significantly greater in SG neurons isolated from septic rats compared with control neurons, but NOP receptor mRNA levels remained unchanged during the 72-h period. ConclusionsOur study demonstrates the cecal ligation and puncture model–induced temporal upregulation of components within the NOP receptor signaling pathway in rat sympathetic neurons. As SG neurons provide the main sympathetic input to the heart, an increased Noc release and potency during sepsis may compromise cardiovascular function.

Blood pressure regulation: every adaptation is an integration?

This focused review serves to explore relevant issues in regard to blood pressure regulation and by doing so, provides the initial stimulus paper for the Thematic Review series "Blood Pressure Regulation" to be published in the European Journal of Applied Physiology over the coming months. In this introduction, we highlight how variable normal blood pressure can be and challenge the reader to take another look at some key concepts related to blood pressure regulation. We point out that there is frequently an underappreciated balance between peripheral vasodilation and systemic blood pressure regulation and ask the question: are changes in blood pressure, in effect, reasonable and integrated adaptations to the physiological challenge at hand? We conclude with the idea that blood pressure regulatory systems are both flexible and redundant; ensuring a wide variety of activities associated with life can be accompanied by a perfusion pressure that can serve multiple masters.

Circulating anandamide and blood pressure in patients with obstructive sleep apnea

Obstructive sleep apnea chronically increases blood pressure through sympathetic nervous system activation. In animals, hypertension and sympathetic activity are restrained by cannabinoid receptor activation. Therefore, we hypothesized that increased blood pressure in patients with obstructive sleep apnea is associated with increased circulating endocannabinoid concentrations. Arterial oxygen saturation and apnea/hypopnea episodes were recorded in 29 patients with normal glucose tolerance, 26 patients with type 2 diabetes mellitus, and 21 patients obese subjects without sleep apnea. We determined seated blood pressure, insulin, glucose, and high-sensitive C-reactive protein in the morning, and insulin sensitivity by euglycemic-hyperinsulinemic clamp the next day. Anandamide, the sum of 1-arachidonoylglycerol and 2-arachidonoylglycerol, and oleoylethanolamide were measured in plasma by liquid chromatography-tandem mass spectrometry. Endocannabinoid concentrations in sleep apnea patients were increased compared to obese individuals without disordered nocturnal breathing. Correction for variables of obesity and insulin resistance almost completely abrogated this difference in endocannabinoids. Anandamide strongly correlated with blood pressure in sleep apnea patients (r = 0.60 for SBP and r = 0.58 for DBP, P < 0.001). In multivariate regression analysis, anandamide was a stronger determinant of blood pressure than sleep apnea severity, obesity, insulin resistance, and inflammation. Obstructive sleep apnea patients show positive correlations between blood pressure and venous anandamide concentrations independent of confounding factors. Our data suggest a previously not recognized role of the endocannabinoid system for blood pressure regulation in patients with high risk for hypertension and cardiovascular disease.

Hard‐wired for hypertension? The sympathetic nervous system causing havoc to non‐responders’ blood pressure

Hard‐wired for hypertension? The sympathetic nervous system causing havoc to non‐responders’ blood pressure

DFT Study of the [Cu-Angiotensin II]2+Complex Structure

Angiotensin II (Ang II, an octapeptide hormone: Asp1Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8) has been studied for several decades in investigations of the structure-dependent activity of the renin-angiotensin blood pressure regulation system. Metal ion influences on the biological activity of Ang II have also been investigated. Blood pressure was observed to increase as a result of the influence of Li, Na, Mg, and Ca ions on the renin-angiotensin system. Thus, it was proposed that the alkali (or alkaline-earth) metal ions induced conformational changes in Ang II that led to a conformational structure more suitable for the biological activity of Ang II. However, the Cu ion was observed to reduce blood pressure in a study performed by separate research group. A few different positive ion complexes [Cu-Ang II] have been studied. The Cu binding sites of the [Cu-Ang II] complex were suggested to have a Cu-NNNN geometry in the ATCUN (Amino Terminal Cu(II) and Ni(II)) complex. However, the Cu binding sites in the [Cu-Ang II] complex were suggested to be the oxygen atoms of the carbonyl functional groups. The structure of Ang II has been reported to be S-shaped according to the results of an NMR experiment. This S-shaped structure has two potential metal ion binding pockets (Fig. 1). Different patterns of interaction between metal ions (Mg, Cu, and Ni) and Ang II have been reported as a result of the different fragmentation patterns obtained in an electrospray ionization mass spectrometry (ESI-MS) experiment. The Mg ion was reported to choose the ‘B’ binding pocket (Ile5His6-Pro7-Phe8) in the [Mg-Ang II] complex. However, Cu and Ni ions were reported to choose the ‘A’ binding pocket (Asp1-Arg2-Val3-Tyr4) in the [Cu (or Ni)-Ang II] complexes. The metal ion binding sites of Ang II were reported to be the amide oxygen atoms instead of the deprotonated peptide nitrogen atoms (N−). In the gas phase, the ligand affinities of alkaline earth metal and transition metal ions have been reported based on the results of a collision-induced dissociation (CID) experiment using ESIMS measurement. The present paper focuses on the interaction between a Cu ion and the ‘A’ pocket of the Ang II molecule. The interaction between a Cu ion and the carbonyl oxygen atoms of Ang II is studied in terms of optimized structures obtained from ab initio calculations. The ab initio calculations were performed to determine both the optimized structures and the SCF energies of the [Cu-Ang II] complex. These optimized structures and their SCF energies are reported.