Neuropeptides and endocannabinoid system as regulators of blood pressure in adolescents with primary hypertension
Department of Clinical Biochemistry, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Malopolska, Poland
Department of Pediatric Nephrology and Hypertension, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Malopolska, Poland.
Abstract
Hypertensionis one of the leading causes of cardiovascular disease and premature death worldwide, affecting more than 1.2 billion adults, with a significant part living in low- and middle-income countries. Pediatric hypertension is also a growing concern, with an estimated 4.5% of children in the United States affected. The 2024 European Society of Cardiology guidelines provide updated protocols for diagnosing and treating hypertension in adults, while pediatrics diagnosis is based on age and weight-specific percentiles. The renin-angiotensin-aldosterone system plays a crucial role in blood pressure (BP) regulation, with 2 pathways: classical pathway and alternative pathway. classical pathway increases BP and fluid retention, while alternative pathway counteracts these effects. Neuropeptides such as Nesfatin-1 (Nes-1) and Galanin (Gal), along with the endocannabinoid system, also influence BP regulation. The study focused on adolescents with hypertension, obesity, or combination. From the hospital, 128 patients were recruited to the study. Plasma samples were analyzed for Nes-1, Gal, anandamide (AEA), and 2-arachidonoylglycerol levels. The results showed significantly lower levels of Nes-1 and Gal in the obese hypertensive patients (P = .005 and P = .022 respectively) and obesity groups (P = .022 and P = .035 respectively) compared to the controls. AEA levels did not show significant differences, while 2-arachidonoylglycerol levels were tendential to higher concentration in hypertensive patients. The lower concentration of Nes-1 and Gal can be considered as predictive factors of hypertension in obese patients, with Nes-1 negatively correlated with systolic pressure. Endocannabinoid system, through cannabinoid receptors 1, may also influence BP, though its role requires further research. Understanding these systems could improve the management of hypertension, particularly in pediatric populations.
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Keywords: angiotensin, cardiovascular disease, obesity, pediatric, RAAS
Article notes
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Received 2025 Jul 16; Revised 2025 Oct 30; Accepted 2025 Nov 3; Collection date 2026 May 1.
1. Introduction
Arterial hypertension (AH) is the leading cause of cardiovascular disease and premature death worldwide. An estimated 1.2 billion adults have hypertension. Mostly of them live in low- and middle-income countries. Less than 50% of adults with hypertension are diagnosed and treated.[1] Hypertension in the pediatrics population is also a serious challenge. It is estimated that even 4.5% of children in the United States (US) have hypertension. Up to 15% of the population may be at risk due to abnormal blood pressure (BP).[2] Hypertension is the sustained elevation of BP. In 2024, the European Society of Cardiology introduced the new guidelines for the diagnosis and treatment of hypertension in adults.[3] The diagnosis of hypertension is based on repeated BP measurements. In Europe, the cutoff point is invariably assumed to be 140 mm Hg in systolic blood pressure (SP) and 90 mm Hg in diastolic blood pressure (DP). Between 120 mm Hg and 139 mm Hg SP/ 70 mm Hg and 89 mm Hg DP, the BP is elevated. The new regulations are like the US guidelines. The 2017 US regulation set the cutoff point at 130/80 mm Hg (SP and DP, respectively).[4] In the pediatrics population, normal BP depends on the patient’s age and weight. Therefore, it is impossible to set up a single cutoff point for the entire population. In this case, the diagnosis is based on the percentiles of BP depending on the patient’s age and sex. According to “2016 European Society of Hypertension guidelines for the management of high BP in children and adolescents”, the hypertension is defined as systolic BP and/or diastolic BP persistently at least 95th percentile for sex, age and height measured on at least 3 separate occasions. however, patients > 16 years of age are treated as adults.[5]
The main system that regulates BP is the renin-angiotensin-aldosterone system (RAAS). RAAS is a complex of enzymatic-hormonal cascade that plays a crucial role in regulating BP, fluid balance, and electrolyte homeostasis.[6] RAAS can be divided into 2 opposite pathways. Although the classical pathway (CP) of RAAS is well known, there is a second pathway known as the nonclassical or alternative pathway (AP).[7] The main CP peptides are angiotensin (ang)II and ang IV, and the main AP peptides are ang 1-7 and ang 1-9. Stimulation of the CP leads to increased BP, retention of sodium and water, increased resistance of peripheral blood vessels, and consequently, left ventricular hypertrophy.[8] The AP counteracts overactivity of the CP. AP normalizes BP, relaxes blood vessels, and stops myocardial hypertrophy.[9] In addition to RAAS, BP can be affected by many other systems and factors, for example, neuropeptides (NP) and the endocannabinoid system (ECS).[10,11] The relations of CP and AP with ECS and NP and their influence on BP are poorly understood.
Nesfatin-1 (Nes-1) is a NP that was initially identified for its role in the regulation of appetite and body weight.[12] However, emerging research has suggested that Nes-1 may also play a role in modulating BP.[13] Nes-1 is expressed in various regions of the central nervous system, including the hypothalamus and brainstem, which are key areas involved in the control of cardiovascular function.[14] Nes-1 may influence the activity of the autonomic nervous system, including sympathetic and parasympathetic outflows. Nes-1 receptors are found in vascular smooth muscle cells, indicating a potential direct influence on vascular tone.[15] The peptide may affect blood vessel constriction or dilation, thereby affecting peripheral resistance and BP. Nes-1 is involved in the regulation of various metabolic processes, including glucose metabolism and insulin sensitivity.[16] Metabolic factors can have indirect effects on BP regulation, and the role of Nes-1 in metabolic regulation may contribute to its influence on cardiovascular function.[13] It is important to note that understanding Nes-1’s role in BP regulation remains an area of active research.[17]
Galanin (Gal) is a NP that is widely distributed in the central and peripheral nervous systems and is involved in various physiological processes.[18–21] Some studies have suggested that Gal may influence BP through its interactions with the autonomic nervous system and its effects on vascular tone.[22] The autonomic nervous system plays a crucial role in regulating BP, and Gal has been found in certain areas of the brain that are involved in the control of cardiovascular function.[23,24] Moreover, Gal may have vasodilatory effects, which means that it could help widen blood vessels, potentially affecting BP.[25]
The ECS is a complex signaling system that plays a crucial role in various physiological processes, including the regulation of cardiovascular function. Two well-studied endocannabinoids are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The specific role of the ECS in hypertension involves modulation of vascular tone, heart rate, and fluid balance. In general, endocannabinoids have been associated with vasodilation, which means that they help relax blood vessels and reduce resistance to blood flow.[26,27] ECS can modulate the activity of the sympathetic nervous system, which takes part in the “fight or flight” response and can influence heart rate and BP. Activation of the ECS can reduce sympathetic flow, leading to a decrease in the release of norepinephrine and other neurotransmitters that contribute to an increase in heart rate and BP.[28] The ECS is also involved in the regulation of renal function, including the balance of water and salt, and it has anti-inflammatory and antioxidant properties. Chronic inflammation and oxidative stress may be associated with hypertension.[29]
1.1. Aim of the study
The aim of the study is to determine the impact of selected NPs on BP regulation with respect to CP and AP of RAAS. Also supporting role of ECS in BP homeostasis had be evaluated. It may be of critical value in understanding the mechanism of hypertension pathogenesis because these factors have potential stimulation or inhibitory effects on both RAAS pathways. This has not yet been the subject of research, especially in the group of adolescents.
2. Materials and methods
We recruited adolescents with AH, obesity, and combinations of both factors from the Department of Pediatrics Nephrology and Hypertension, University Children’s Hospital in Krakow. Each patient was recruited based on including and excluding criteria. All patients were recruited to study by medical doctors based on repeaters of BP measurement, interview and medical examinations. Most of patients were referred to the department for further hypertension diagnosis. Only patients with spontaneous AH have been qualified to the study. AH was diagnosed according to the 2016 Pediatrics Hypertension Guidelines developed by European Society of Hypertension. Hypertension was diagnosed based on percentiles ( > 95th for 0–15 years) and SP and/or DP values ( < 140/90, 16 years and older). Any other patient data is collected from their hospital information system. Patients with body mass > 97, percentiles was qualified for the obese group. Fasting blood samples (S-Monovette EDTA K3E/2.6ml, Sarstedt AG & Co.KG, Numbrecht, Northrhine-Westphalia, Germany) were taken in the morning, immediately cooled and centrifuged. Adolescents in the control group were recruited from the families and friends of the study researchers. These adolescents did not have pathological clinical signs or complaints or pharmacological treatment. In the control group, fasting blood samples were drawn in the same procedure as in the study group.
Blood samples were centrifugated and separated EDTA plasma was frozen at −80 centigrade until measurement. The maximum banking time was not longer than 12 months. Peptide concentrations were measured using commercially available enzyme-linked immunosorbent assay immunoassays. Nes-1 assay range: 7.8 ng/ml–500 ng/ml, Gal assay range: 6.25 ng/ml–200 ng/ml, (Qayee BioTechnology Co., Ltd. Shanghai, China) and AEA assay range: 3.13 ng/ml–200 ng/ml, and 2-AG assay range: 4.69 ng/ml–300 ng/ml (ELK Biotechnology CO., Ltd., Sugar Land). Manufacturers declare that there is no significant cross-reactivity and intra coefficient of variation < 15%. The samples were slowly defrosted. The first step was the transfer of the samples from −80 centigrade to −20centigrade for a night; later they were thawed in water with ice. The 5-time sample dilution was proved for the Nes-1 and Gal kits.
Details describing the measurements of ang II, ang IV, ang 1-7, and ang 1-9 are summarized in the previous study.[30]
The assay procedures were performed according to the manufacturer’s manuals using a Bio-Rad washer and plate reader (Hercules, CA).
The study protocol was approved by the Jagiellonian University Bioethical Committee (approval no. 1072.6120.210.2022) according to the Declaration of Helsinki and informed consent was obtained from all guardians of the patient and all patients over 16 years of age enrolled in the study.
Statistical analysis was performed using IBM SPSS Statistics v.29 (IBM Corporation, Armonk, NY). The concentrations of Nes-1, Gal, AEA, and 2-AG were expressed as median values, Q1 and Q3. Normality was checked using the Shapiro–Wilk test in each group. The Kruskal–Walli test with Bonferroni post hoc was performed for comparisons between groups. The Spearman rank correlation and linear regression were also performed.
3. Results
We have studied patients with confirmed AH and normal body weight, obese patients with confirmed AH, and obese patients with normal BP. Fifty-two healthy children with normal body mass index (BMI) and BP were studied. All characteristics of the patients are summarized in Table 1.
| Group | N | Age [yr] | BMI [kg/m2] | SP [mm Hg] | DP [mm Hg] |
|---|---|---|---|---|---|
| Hypertension | 28 | 15.05 ± 2.98 | 21.75 ± 3.44 | 135 ± 16 | 79 ± 11 |
| Hypertension + obesity | 17 | 13.95 ± 3.79 | 29.89 ± 4.64 | 138 ± 19 | 74 ± 14 |
| Obesity | 29 | 13,50 ± 3.39 | 28.40 ± 5.59 | 114 ± 10 | 68 ± 9 |
| Control | 52 | 12.95 ± 3.69 | 18.63 ± 3,9 | 112 ± 11 | 66 ± 10 |
3.1. Nes-1
Plasma Nes-1 concentrations differ statistically between the analyzed groups (P = .001). The median, Q1 and Q3, respectively, was 185.28 [167.62–219.36] ng/mL in hypertension, 179.98 [164.59–189.54] ng/mL in hypertension and obesity, and 187.23 [170.30–205.81] ng/mL in obesity. The concentration of Nes-1 in the control group was 206.42 [187.90–223.58] ng/ml. Nes-1 concentration was lower in the hypertension + obesity group and the obesity group compared to the control group. The exact statistical values was shown on Figure 1.
3.2. Gal
Plasma Gal concentrations also differ statistically between the analyzed groups (P = .009). The median, Q1 and Q3, respectively, was 86.40 [75.30–102.87] ng/ml in hypertension, 80.52 [72.15–92.83] ng/ml in hypertension and obesity, and 84.03 [72.83–97.02] ng/ml in obesity. Gal concentration in the control group was 91.69 [86.1–105.88] ng/ml. Gal concentration was significantly lower in the hypertension + obesity group and the obesity group compared to the control group. The exact statistical values was shown on Figure 2.
3.3. AEA
Plasma AEA concentrations did not differ statistically in the analyzed groups (P = .316). The median, Q1 and Q3, respectively, were 28.43 [12.60–50.40] ng/mL in hypertension, 28.35 [15.26–45.79] ng/mL in hypertension and obesity, and 29.40 [11.50–42.26] ng/mL in obesity. The AEA concentration in the control group was 32.14 [21.51–48.54] ng/ml. As shown on Figure 3.
3.4. 2-AG
Plasma 2-AG concentrations differ statistically in the analyzed groups (P = .023). The median, Q1 and Q3, respectively, was 417.80 [392.91–467.70] ng/mL in hypertension, 445.31 [398.56–478.92] ng/mL in hypertension and obesity, and 401.70 [367.96–456.40] ng/mL in obesity. The AEA concentration in the control group was 383.64 [330.53–444.25] ng/ml. The 2-AG shown tendential to higher concentrations in the hypertension group and in the hypertension + obesity group compared to the control group. As shown on Figure 4.
The correlations of ECS, NP and RAAS with SP and CP are summarized in Table 2. The r and R2 are shown when the P value is significant. Among the parameters analyzed, only ang II and Nes-1 have shown a significant correlation with SP. In both situations, can be observed a negative correlation.
| Nes-1 | Gal | AEA | 2-AG | Ang II | Ang IV | Ang 1-7 | Ang 1-9 | |||
|---|---|---|---|---|---|---|---|---|---|---|
| SP | P | .049 | .191 | .949 | .112 | .034 | .249 | .494 | .084 | |
| r | −0.178 | ns | ns | ns | −0.193 | ns | ns | ns | ||
| R 2 | 0.03 | ns | ns | ns | 0.04 | ns | ns | ns | ||
| DP | P | .163 | .651 | .911 | .093 | .539 | .5 | .350 | .213 | |
| r | ns | ns | ns | ns | ns | ns | ns | ns | ||
| R 2 | ns | ns | ns | ns | ns | ns | ns | ns | ||
Analysis in specific groups showed the strongest correlation and regression in the hypertension group. All details are summarized on Figure 5 and in Table 3.
| Hypertension | Hypertension + obesity | Obesity | Control | |
|---|---|---|---|---|
| Ang II–SP | 0.072 | 0.024 | 0.050 | 0.002 |
| Nes-1–SP | 0.105 | 0.006 | 0.037 | 0.029 |
3.5. European Society of Cardiology and NP as regulatory factors of BP
A correlation analysis between ECS, NP, and RAAS was performed. The RAAS components were described in an earlier study.[30] The analysis was performed separately for both RAAS pathways for important angiotensin peptides. The main CP peptides are ang II and ang IV, the main AP peptides are Ang 1-7 and ang 1-9. Significant correlation was observed for Nes-1, Gal, and 2-AG.
Nes-1 showed significant correlations with Ang II, Ang IV, Ang 1-7, and Ang 1-9. The correlations are summarized in Table 4.
| Classical pathway of RAAS | Alternative pathway of RAAS | |||
|---|---|---|---|---|
| Ang II | Ang IV | Ang 1-7 | Ang 1-9 | |
| r | 0.638 | 0.718 | 0.477 | 0.759 |
| P | < .001 | < .001 | < .001 | < .001 |
| R 2 | 0.434 | 0.516 | 0.213 | 0.576 |
For correlation Nes-1 and Ang II correlation, by analyzing the individual study groups, it was found that the highest correlation is in the hypertension group and in the hypertension and obesity group. For correlation Nes-1 and Ang IV analyzing of individual study group shows the highest correlation for hypertension group. For the correlation, the Nes-1 and Ang 1-7 analyzed in the individual study group show the highest correlation, also for the hypertension group. For correlation Nes-1 and Ang 1-9 correlation analysis of the individual study group shows the highest correlation also for the hypertension and obesity group. All details are shown in Figure 6 and Table 5.
| Hypertension | Hypertension + obesity | Obesity | Control | |
|---|---|---|---|---|
| Ang 1-7 | 0.523 | 0.311 | 0.307 | 0.118 |
| Ang II | 0.564 | 0.545 | 0.249 | 0.200 |
| Ang 1-9 | 0.425 | 0.562 | 0.388 | 0.373 |
| Ang IV | 0.726 | 0.277 | 0.435 | 0.171 |
Gal showed significant correlations with Ang II, Ang IV, Ang 1-7, and Ang 1-9. The correlations are summarized in Table 6.
| Classical pathway of RAAS | Alternative pathway of RAAS | |||
|---|---|---|---|---|
| Ang II | Ang IV | Ang 1-7 | Ang 1-9 | |
| r | 0.833 | 0.814 | 0.558 | 0.629 |
| P | < .001 | < .001 | < .001 | < .001 |
| R 2 | 0.694 | 0.663 | 0.328 | 0.396 |
Gal showed a strong correlation with peptides from the CP and a weak correlation with peptides from the AP. In separated groups Gal presents a strong correlation in hypertension and hypertension and obesity group. Also, a strong significant correlation between Gal and Ang IV was observed. In the separated groups, there is a strong positive correlation in the hypertension group. Remarkably interesting is the strong correlation in the control group. The correlation between Gal and Ang 1-7 is the strongest in the hypertension + obesity group. The lowest correlation but still significant, correlation is in control subgroups as shown on Figure 7 and Table 7.
| Hypertension | Hypertension + obesity | Obesity | Control | |
|---|---|---|---|---|
| Ang 1-7 | 0.584 | 0.622 | 0.331 | 0.257 |
| Ang II | 0.711 | 0.762 | 0.624 | 0.516 |
| Ang 1-9 | 0.425 | 0.562 | 0.388 | 0.373 |
| Ang IV | 0.752 | 0.334 | 0.474 | 0.759 |
3.6. 2-AG
2-AG shown significant correlations with Ang II, Ang IV, Ang 1-7, and Ang 1-9. Correlations are summarized in Table 8.
| Classical pathway of RAAS | Alternative pathway of RAAS | |||
|---|---|---|---|---|
| Ang II | Ang IV | Ang 1-7 | Ang 1-9 | |
| r | −0.273 | −0.300 | −0.241 | −0.354 |
| P | .003 | .001 | .008 | < .001 |
| R 2 | 0.075 | 0.09 | 0.058 | 0.125 |
2-AG presents a negative significant correlation with all angiotensin peptides, in RAAS pathways. The strongest correlation is for Ang 1-9. There is no clarifying correlation difference between CP and AP as shown in Figure 8 and Table 9. Similar changes can be observed in regression in specific groups. Linear regression analysis showed that 2-AG is dependent on CP angiotensin peptides, especially in the hypertension group. On the other hand, in AP angiotensin peptides are correlated with the obesity group.
| Hypertension | Hypertension + obesity | Obesity | Control | |
|---|---|---|---|---|
| Ang 1-7 | 0.022 | 0.039 | 0.110 | 0.102 |
| Ang II | 0.145 | 0.001 | 0.036 | 0.048 |
| Ang 1-9 | 0.056 | 0.027 | 0.173 | 0.005 |
| Ang IV | 0.173 | 0.063 | 0.032 | 0.134 |
4. Discussion
This is the first study to comprehensively describe various systems in regulating BP in specific group of patients—adolescents.
4.1. Nes-1
Most of published studies showed a lower Nes-1 concentration in obese patients compared to normal weight patients. Also in our study, Nes-1 concentration was significantly lower in obese patients and obese patients with hypertension than lean control group. Negative correlation trend of Nes-1 with SP confirmed its role in hypertension.
In 2019 Gunes et al evaluated the impact of Nes-1 on the prediction of hypertension in 87 obese children. In their study, the fasting concentration of Nes-1 was higher in hypertensive obese children than in normotensive children (P = .007). In our study, we did not observe significant differences in Nes-1 concentration between the obese children with and without. The possible cause of this discrepancy could be that in Gunes et al study the BMI value was higher in the obese hypertension group than in normotensive obese children (P < .001) while in our study the BMI value was similar in both obese groups.[31] The relation between Nes-1 and body mass was observed by Dios et al, Dokumacioglu et al and Abaci et al.[32–34] In these studies, median Nes-1 concentration was lower in obese children than in normal weight patients, in the Abaci et al studies the difference was significant (P = .001).[34] Also, in the study by Kim et al in the pediatrics population, the concentration of Nes-1 was lower in the obesity group than in the control group with proper BMI. Kim et al also found a negative correlation between Nes-1 and BMI (r = −0.33; P = .02), similarly to our study, a negative correlation between Nes-1 concentration and BMI was developed (r = −0.233; P = .01).[35]
The lower concentration of Nes-1 in obese individuals confirmed its key role in the regulation of food intake in obese individuals. However, the role of Nes-1 in the development of hypertension may still be unknown. In some studies, Nes-1 was typed as a predictive biomarker of hypertension in obese patients considering a negative correlation with SP.
4.2. Gal
In our study, Gal concentration was significantly lower in obese patients with hypertension and in obese patients as compared to lean control group. These data are opposite to the results of Fang et al and Kravchun et al. In their studies, the obese with and without hypertension had a higher Gal concentration than the lean control.[36,37] In Fang et al obese patients with hypertension had a lower Gal concentration than the obese without hypertension (P < .01).[36] According to Kravchun et al the Gal level corresponded to the hypertension grade. Fang et al, as well as Kravchun et al suggested that Gal may be a new predictive biomarker of hypertension development and/or cardiovascular disease in obese patients. The discrepancy between our results and listed above may be due to the age of the patients, as in the study by Fang et al, the mean patient age was > 30 years, however also Acar et al detect had higher Gal concentration in obese children than lean control.[38] There are no more studies describing Gal concentrations in obese and lean children. In our study Gal strongly correlate with CPs peptides—with Ang II in all patients, especially in patient with hypertension.[30] The second peptide of CP Ang IV also shows similar relation. The recent papers is suggested, that decreased Gal concentration leads to decline fat consumption, and in consequence, decline body mass.[18] So, in the wider scope Gal links food intake with some kind of compensatory mechanisms of hypertension.
4.3. Endocannabinoids
The endocannabinoids system is considered a new BP regulator. In the study by Gimenez et al in rats, AEA strongly decreased BP after 4 weeks of therapy. Researchers used a nano-formulated AEA at intraperitoneal injections. They suggested that AEA may inhibit angiotensin receptor type I.[39] In addition, Gimenez et al in 2023 continuing research on rats, confirmed their previous observations about the hypotensive effect of AEA, also after intravenous administration.[40] Hypotensive effect is fast (even 2 hours) and includes mechanisms such as increase in the natriuretic and diuretic effect. In the study by Wheal et al in rats, AEA also presented an antihypertensive effect. A main mechanism is vasorelaxation through cannabinoid receptors 1 (CB1) activation.[41] Guo et al observed similar action in which aortic relaxation was observed after AEA administration in hypertensive rats.[42] On the other hand, the study by Golosova et al showed that prolonged stimulation of CB receptors may results in kidney damage and hypertension in salt-sensitive rats. The researchers suggest that transforming growth factor beta1/mothers against decapentaplegic homolog 3 signaling pathway may be involved.[43] In the study by Batkai et al in spontaneously hypertensive rats, the CB1 antagonist increases BP and contractile performance of left ventricular. Preventing the degradation of the endocannabinoid AEA by an inhibitor of fatty acid amidohydrolase reduces BP, cardiac contractility, and vascular resistance to levels in normotensive rats.[44] AEA and 2-AG are agonists of the CB1 receptor. According to Jarai et al, the prolonged effect of 2-AG in rodents is questionable to its rapid degradation in blood by lipase and observed cardiovascular effects of 2-AG are produced by an arachidonate metabolite through a non cannabinoid mechanism.
Human studies confirmed an inotropic property of ECS. In the study by Bonz et al, AEA and synthetic analogues decrease contractile performance in human atrial muscle through CB1 receptors.[45] Sarzani et al presented that Rimonabant, the CB1 receptor antagonist, causes a decrease in BP, probably in the inotropic and weight-loss mechanism in obese patients.[46]
The relationship between ECS and angiotensin peptides is poor and not clearly understood. In the study by Miklos et al on rat models, activations of the angiotensin II receptor type 1 signaling pathway by Ang II cause the release of 2-AG and activation of the CB1 receptor.[46] In our study concentrations of 2-AG and AEA were higher in hypertension group. 2-AG negatively correlated with all angiotensin peptides on both pathways, but AEA didn’t (might be due to fast degradation in vivo). Anyway we suppose that ECS may be a target in the pharmacological treatment of hypertension and obesity.
The major limitations of the study may be involved with high biological variations of analyzed factors. In case of ECS, NP and angiotensin peptides we can observed changes in secretion related to circadian rhythm, food intake and stress.
5. Conclusions
This is a preliminary study. In the regulation of BP are involved many systems like RAAS, ECS and NP. While engagement of RAAS is clearly understood, such impact of other systems requires further research. Systems like ECS and NP act in support of the main regulations. Nes-1 and Gal are NP involved in appetite regulation, which may affect the development of obesity-dependent hypertension. The decreased concentration of Nes-1 should inhibit consumption. In our study a lower Nes-1 concentration is observed in all study groups, statistically significant in obese hypertension patients and normotensive obese patients. The effect is stronger in hypertension obese patients. Nes-1 can be usefulness in treatment hypertension and obesity. Someone postulated a using Nes-1 as a hypertension predictor in obese patients, but it requires confirmation in another study.
In our study Gal presented related results to Nes-1. In the other analyzed studies Gal concentration was higher in hypertension group compared to normotensive patients. Gal as a regulating hormone impact on fat consumption. Lower concentration in obese normotensive and hypertensive patients shown an attempt of obese and hypertension counteract.
The functions of ECS are still not fully understood. On the one hand, CB1R cannabinoids can reduce BP. On the other hand, in our study, ECS such as AEA and 2-AG did not show any significant differences. It may be the result of ECS that rapidly degenerate. Admission CB1R agonist like 2-AG has shown hypotensive activity and may be a part of antihypertensive therapy but this requires a further research.
The future research should be focused on minimizing the impact of preanalytical phase and biological variation on results. Also patients should be examined in 1 time point without any treatment or diet restriction.
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Footnote Group
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Footnote Group
Contributor Information
Magdalena Wójcicka, Email: magdalena.wojcicka@uj.edu.pl.
Dorota Drożdż, Email: dorota.drozdz@uj.edu.pl.
Przemysław J. Tomasik, Email: p.tomasik@uj.edu.pl.
References
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