{"id":54307,"date":"2023-12-31T10:20:41","date_gmt":"2023-12-31T10:20:41","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=54307"},"modified":"2024-01-05T07:06:09","modified_gmt":"2024-01-05T07:06:09","slug":"impact-of-angiotensin-receptor-blockers-on-angiotensin-iii-and-leptin-in-rabbits","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol16no4\/impact-of-angiotensin-receptor-blockers-on-angiotensin-iii-and-leptin-in-rabbits\/","title":{"rendered":"Impact of Angiotensin Receptor Blockers on Angiotensin Iii and Leptin in Rabbits"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

The Renin\nAngiotensin system (RAS) is a component of the renal system that is independent\nof the peripheral RAS. It plays a role in regulating sodium excretion and blood\npressure1<\/sup>. The entirety of the forerunners of angiotensin (Ang)\npeptide union is situated inside the proximal renal tubule2<\/sup>,\ncounting angiotensinogen, renin, and Ang changing over protein messenger\nribosome nucleus acid (mRNA)3<\/sup>. The Ang III and Ang II convergences\nare more prominent than could explained solely by the equilibration with the\ncircling focuses4<\/sup>. These discoveries recommend that significant\nimpacts are applied by privately produced angiotensins5<\/sup>.\nFurthermore, the two significant receptor subtypes that intercede with activities\nof RAS, the type 1 Angiotensin receptor (AT1R) and the type 2 Angiotensin\nreceptor (AT2R) are both present in renal proximal tubule cells, predictable\nwith an essential part for rounded as paracrine substances, angiotensins play a\nrole in the regulation of renal capacity6<\/sup>.<\/p>\n\n\n\n

Angiotensin\nreceptor blockers (ARBs) are designed to bind to the Ang II receptor, which has various actions, including vasoconstriction, the production of\naldosterone, cytokine, reactive-oxygen-species formation, and mitogenic\nactivity 7<\/sup>.<\/p>\n\n\n\n

Angiotensin III\nis one of the N-terminal angiotensin debasement results of Ang II, which\nimparts a portion of its properties to Ang II, including chemotaxis and\ncreation development factors and chemokines. Ang III showed comparable\ncapacities to Ang II. The two peptides partake in the CV and renal capacities,\nanimating aldosterone synthesis and diminishing renal bloodstream and renin\ndischarge circulatory strain8<\/sup>. ANG III contributes to the\ndevelopment of transcription factors during physiological conditions. Apart\nfrom stimulating the production of ANG1 receptors, it also binds to the AT2\nreceptors, which are known to suppress the expression of certain transcription\nfactors. It has been observed that the tonic inhibition of the AT2 receptors\naffects the different neuronal populations9<\/sup>.<\/p>\n\n\n\n

Leptin is a\nhormone that has acquired tremendous advances in the comprehension of CVD, and\nits primary capacities incorporate; angiogenesis, pulse control, vascular\nhemostasis, irritation, immune reaction, and metabolic guidelines10, 11<\/sup>. Leptin (LEP) contributes to\ncontrolling the resting metabolic rate12<\/sup> and blood pressure through\nits actions in the arcuate nucleus13<\/sup>. The RAS and AT1R within the brain14<\/sup> are likewise\nengaged with the control of resting metabolic rate and pulse6<\/sup>,\nregardless of whether this guideline covers LEP activities is indistinct15<\/sup>.\n<\/p>\n\n\n\n

This study was performed to find out the impact of ARBs (Losartan, Telmisartan, and Candesartan) on Ang III and LEP in rabbits by the assessment of the following:<\/p>\n\n\n\n

The effect of Losartan, Telmisartan, and Candesartan on Angiotensin III.<\/p>\n\n\n\n

The effect of Losartan, Telmisartan, and Candesartan on Leptin.<\/p>\n\n\n\n

Macroscopic and histopathologic study.<\/p>\n\n\n\n

Correlation of Angiotensin III with Leptin, and the study parameters.<\/p>\n\n\n\n

Study Methods<\/strong><\/strong><\/p>\n\n\n\n

Setting<\/strong><\/p>\n\n\n\n

The study was carried out at Al-Isra University’s Faculty of\nPharmacy-experimental animal house, from January 2020 to October 2020. Based on\nan ethically approved protocol (SRES\/21\/02\/002). All\nchemicals, reagents, and ELISA kits used in this study with the highest purity,\nfrom USA, Canada, and India origin.<\/a><\/p>\n\n\n\n

Rabbits and housing<\/strong><\/p>\n\n\n\n

The forty male rabbits were housed in a cage and fed and cared for according to the laboratory’s conditions in the university’s animal house. All the animals in the house are kept in a separate cage. The rabbits were allowed to adjust to their housing conditions a week before the start of the study. They were kept in a standard room and provided with free tap water and rodent chow. The animals were also kept on a 12-hour light cycle and exposed to humidity at a temperature of 25 degrees Celsius.<\/p>\n\n\n\n

All\nthe experiments related to the care and use of laboratory animals were carried\nout according to the NIH’s guidelines (NIH-Publications Number 85 to 23,\nrevised-1985). <\/p>\n\n\n\n

Experimental design & Study groups<\/strong><\/p>\n\n\n\n

A total of 40 Oryctolagus cuniculus rabbits were divided randomly statistically by\nMicrosoft Excel into four groups, each consisting of 10 rabbits as follows:Oryctolagus cuniculus rabbits were also allowed to eat and drink ad libitum, and they\nwere monitored for their steady weight throughout the experiment. The treated\ngroups were administered\ndrugs I.P. once daily for 10 days. A solution of 1 ml (DMSO was used as a solvent). The forty rabbits were divided randomly into four groups (each 10):<\/p>\n\n\n\n

Group I: Losartan treated 0.7 mg\/kg\/day. <\/p>\n\n\n\n

Group II: Telmisartan treated 0.6 mg\/kg\/day. <\/p>\n\n\n\n

Group III: Candesartan treated 0.1 mg\/kg\/day. <\/p>\n\n\n\n

Group IV: Control (vehicle-treated)<\/p>\n\n\n\n

Dosage\nand sample preparation:<\/strong><\/strong><\/p>\n\n\n\n

Losartan, Telmisartan, and Candesartan (from Sigma Aldrich) solution was prepared by reconstitution of Losartan, Telmisartan, and Candesartan powder with DMSO daily under sterile conditions before injection.<\/p>\n\n\n\n

The\nrabbits were Blood collected from the Jugular vein. Then (3ml) of Blood was transferred\nto a serum (without EDTA) tube. Blood was at once centrifuged at 3000 Revolutions\nper minute (RPM) for 20 min. The serum was then pipetted to Eppendorf and refrigerated\nat -70 degrees Celsius. The rabbits’ body weight was monitored before and after\nthe duration of the study. The various drugs used in the study, such as\nTelmisartan, Losartan, or Candesartan, were then given to separate groups of\nrabbits. They were given prescribed treatment doses according to their\nconditions.<\/p>\n\n\n\n

The rabbits were given a 24-hour extension to their\nlast dose. They were then collected from their Jugular vein and placed into a\nserum tube, which was centrifuged at 3,000 revolutions per minute. The serum\nwas then separated using a pipette and placed at Eppendorf under the cover of\nparafilm. After the animals’ groups were dissected, their tissues and organs\nwere then dried and placed in a 10% buffered formalin solution.<\/p>\n\n\n\n

Rabbit Ang III & Rabbit LEP ELISA Kits<\/strong><\/p>\n\n\n\n

For Both Ang III & LEP follow the manufacturer’s instructions.<\/p>\n\n\n\n

Macroscopic & Histopathologic\nExamination<\/strong><\/p>\n\n\n\n

Organ specimens, such as kidney, liver, and heart, were collected and fixed using immersion in 10% formalin followed by the addition of Xylene, paraffin wax, and a clearing agent. The tissues were then embedded with paraffin wax to form a block. The blocks were then separated using a microtome and placed on slides. They were then stained with eosin and hematoxylin to examine tissue damage, inflammation, and morphological changes.<\/p>\n\n\n\n

Statistics analysis<\/strong><\/p>\n\n\n\n

The data collected during the study were analyzed using the SPSS 24 software. The effect size and sample size calculations were then carried out using the G*Power software. A statistical analysis technique was then used to compare the means of the two groups. A sample-by-sample comparison procedure was also carried out to examine the differences in the mean values between the two groups. ANOVA was then performed to analyze the variance in the mean values. The results of the study were then analyzed using the Pearson correlation coefficient. The strength of the correlation was then evaluated to see how significant it was.<\/p>\n\n\n\n

Results<\/strong><\/strong><\/p>\n\n\n\n

The effect of Losartan, Telmisartan, and Candesartan on Ang III<\/strong><\/p>\n\n\n\n

The\nserum level\nof Ang III was decreased significantly\n(P<0.05) in tested groups; G I: Losartan treated at 0.7 mg \/kg\/day, G II: Telmisartan treated at\n0.6 mg \/kg\/day, and G III: Candesartan treated 0.1 mg \/kg\/day, highly significant difference compared to\nbaseline and control with 95% CI (P=0.0002). However, a non-significant decrease in the\ncontrol group IV compared to the baseline, as shown in Figure 1.<\/p>\n\n\n\n\n\n
\"\"<\/td>\nFigure 1:<\/strong> The serum level of Ang III in tested groups. The serum level of Ang III was decreased significantly (P<0.05) in tested groups;<\/strong>

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The effect of <\/strong>Losartan, Telmisartan, and Candesartan on <\/strong>LEP<\/strong><\/strong><\/p>\n\n\n\n

The\nserum level\nof LEP was decreased significantly\n(P<0.05) in tested groups; G I and II while G III showed a highly significant difference compared to\npre-values with\n95% CI (P=0.0002). However,\na non-significant difference in the control group IV compared to the baseline,\nas shown in Figure 2.<\/p>\n\n\n\n\n\n
\"\"<\/td>\nFigure 2:<\/strong> The serum level of LEP in tested groups. The serum level of LEP was decreased significantly (P<0.05) in tested groups;<\/strong>

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Macroscopic and histopathologic study<\/strong><\/strong><\/p>\n\n\n\n

The ARBs (Losartan, Telmisartan, and Candesartan) efficacy on the rabbit\u2019s weight<\/strong><\/p>\n\n\n\n

The rabbit\u2019s weight was measured (0, 3,\n7, 11) days for all tested groups during the study period starting from day zero to day 11. The average weight for the groups (I,\nII, III) showed a non-significant slight decrease while group IV showed no\ndifference in the rabbit\u2019s weight compared to baseline, as in Figure 3. <\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 3:<\/strong> The average rabbit\u2019s weight during the study period. The average weight for <\/strong>groups (I, II, III) showed a non-significant slight decrease while group IV (P=0.06)<\/strong>.<\/strong><\/p>\n

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The ARBs (<\/strong>Losartan, Telmisartan, and Candesartan) <\/strong>efficacy\non the <\/strong>food consumption<\/strong><\/strong><\/p>\n\n\n\n

The food consumption for animals was measured daily\nduring the study period. The daily average food intake for the treated groups\n(I, II, III) was a non-significant slight decrease, while group IV showed no\ndifference in food intake. Both are non-significant (P=0.06), as presented in\nFigure 4.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure <\/strong>4:<\/strong> Rabbit\u2019s food consumption in studied groups during the study period. The average for groups (I, II, III) showed a non-significant slight decrease while group IV (P=0.06).<\/strong><\/p>\n

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The Microscopic feature<\/strong><\/p>\n\n\n\n

Histopathology of the heart<\/strong><\/p>\n\n\n\n

Histopathological studies of the groups’ heart sections; G (I, II, IV) were normal, as shown in Figures (5A-C). While there was congestion blood vascular in G III shown in Figure 5D for all groups, there was no necrosis and no inflammation. <\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

 <\/strong>Figure 5: A.<\/strong> The heart section of the treated animals\u2019 control (DMSO) group [G IV]. G IV was normal with no necrosis and no inflammation. B. Heart section of treated animals group Losartan (G I).<\/strong><\/p>\n

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Histopathology of the Liver<\/strong><\/p>\n\n\n\n

Histopathological studies of liver sections of the studied groups; G I, II, and IV were normal shown in Figures (6 A-C) except for G III; there was congested blood vascular shown in Figure 6 D. All groups showed no necrosis or inflammation.  <\/strong><\/p>\n\n\n\n\n\n
\"\"<\/td>\nFigure 6: A.<\/strong> Section of the liver in tested control (DMSO) group [G IV]. G IV was normal with no necrosis and no inflammation. <\/a>B. Section of the liver in tested group Losartan (G I). <\/strong>

<\/p>\n

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Histopathology of the Kidney<\/strong><\/p>\n\n\n\n

Histopathological studies of the kidney sections of the studied groups; G (I, II, and IV) were normal shown in Figures (7 A-C), with no pathological changes (necrosis or inflammation), G III showed congestion blood vascular only shown in Figure 7 D. <\/p>\n\n\n\n\n\n
\"\"<\/td>\nFigure 7: A.<\/strong> Normal Kidney section in tested control (DMSO) group [G IV]. G IV was normal with no necrosis and no inflammation.<\/a> B. Normal Kidney section in tested group Losartan (G I). <\/strong>

<\/p>\n

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Correlation study<\/strong><\/p>\n\n\n\n

Pearson\u2019s correlation coefficient\n(r) was used to show the correlation of serum biomarker Ang III and LEP levels to the studied parameters.\nBody weight and food consumption of Oryctolagus\ncuniculus rabbits for all tested groups were assessed and analyzed according\nto their r with significance, and the correlation of Ang III to LEP.<\/a><\/p>\n\n\n\n

Analysis of <\/strong>Ang III<\/strong>\ncorrelation to weight and food consumption<\/strong><\/p>\n\n\n\n

All samples were measured within\nthe same experiment in studying the correlation. Analysis of serum Ang III to weight correlation showed a highly significant strong\npositive correlation between rabbit\u2019s weight post-treatment & serum Ang\nIII\nconc.; r =  0.9778, P = 0.0001, as shown in Figure 8 A.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 8A:<\/strong> The correlation analysis between serum <\/strong>Ang III<\/strong> and weight.<\/strong><\/p>\n

<\/p>\n

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Concerning the correlation of serum Ang III to food consumption, a highly significant strong\npositive-correlation between both parameters, r =  0.957, p =  0.002, as shown in Figure 8 B. <\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 8: B.<\/strong> The correlation analysis between serum <\/strong>Ang III<\/strong> and food consumption.<\/strong><\/p>\n

<\/p>\n

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Analysis\nof <\/strong>LEP<\/strong>\ncorrelation to weight and food consumption<\/strong><\/p>\n\n\n\n

A weak, non-significant positive-correlation\nof serum LEP to weight, r= 0.255, P= 0.06. The same was observed in the\ncorrelation of serum LEP to food consumption. There is a weak, non-significant\npositive-correlation, r = 0.322, p = 0.07, Figures (9 A & B)\nrespectively. <\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

<\/a><\/a>Figure 9A:<\/strong> The correlation analysis of <\/strong>LEP<\/strong> and weight.<\/strong><\/p>\n

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Figure 9B:<\/strong> The correlation analysis of <\/strong>LEP<\/strong> and food consumption.<\/strong><\/p>\n

<\/p>\n

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Correlation analysis of Ang III and LEP<\/strong><\/p>\n\n\n\n

Pearsons-correlation analysis\nshowed weak non-significant positive-correlation between the tested groups’\nserum Ang III & LEP levels, correlation coefficient (r = 0.047, P= 0.06), as shown in Figure 10.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 10: The correlation analysis between serum Ang III and LEP.<\/strong><\/p>\n

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Discussion<\/strong><\/p>\n\n\n\n

Ang III similarly mediates several physiological\nfunctions to Ang II by activation of AT1Rs. It is important to note that the\nheptapeptide Ang III is produced from Ang II by the enzyme APA. Thus, the two\npeptides are remarkably similar (one amino acid difference) in structure16<\/sup>. The Ang III actions are the result of the interactions between the\nAT1R and the AT2R. These actions have fueled the debate about the physiological\nrelevance of the RAS’s peptides. Some studies suggest that Ang III can be the\ntrue agent of the RAS in controlling blood pressure17, 18<\/sup>. also\nvasopressin release19<\/sup>. Amastatin [selective APA inhibitor] was added\nto block the AR, but this inhibitor was not able to prevent the Ang III\nresponse20<\/sup>. The effects of Ang III on different conditions,\nincluding kidney function and blood pressure, were similar to those of Ang II21<\/sup>.<\/p>\n\n\n\n

This study is the first to\nassess the effect of ARBs (Losartan,\nTelmisartan, or Candesartan) on Ang III and LEP. ARBs can be made by blocking the AngII-AT1R interaction, which\nsome believe acts as a mediator between Ang II and its negative effects on the\nCV22<\/sup>. Compared to ACEIs, ARBs are more efficient at restricting the\nRAS blockade. This mechanism is independent of the formation pathway of AngII23<\/sup>.<\/p>\n\n\n\n

Forty Oryctolagus cuniculus male rabbits were utilized to evaluate the efficacy of Losartan, Telmisartan, and Candesartan as ARBs drugs on Ang III and LEP. It was noticed that the serum Ang III decreased in the groups G I: Losartan treated at 0.7 mg \/kg\/day, G II: Telmisartan treated at 0.6 mg \/kg\/day, and G III: Candesartan treated at 0.1 mg \/kg\/day, but non-decreased in the control (DMSO) group IV. However, the decrease was somewhat noticeable in Group III, and Ang II and Ang III could stimulate aldosterone release. However, this is one of the factors that lead to CVD. ARBs are well-known for treating CVD24<\/sup>. The present study is consistent with the earlier studies in that Losartan and Telmisartan act more on the AT1R and Candesartan act on the AT1R and AT2R25<\/sup>. Thus, it was explained that the level of Ang III reduced significantly in group three in comparison to groups one and two.<\/p>\n\n\n\n

Although Ang-I is biologically inactive, its metabolites, Ang II, and Ang III, are known to mediate dipsogenic and pressor effects through the AT1 and AT2 receptor categories. Both compounds are full agonists of the two receptor types26, 27<\/sup>. A proposed counter-regulator axis between the Ang II-Ang III and AT1 receptors has been presented, which includes ACE2 and Ang (1-7). It is believed that this system promotes various actions, such as antiproliferative, vasodilation, antifibrosis, and antihypertrophic28, 29<\/sup>. Albeit insufficient information has been amassed on Ang III and AT2R, it has been written down that Ang III intervenes natriuretic reaction through AT2R under foundational AT1R barricade30, 31<\/sup>.<\/p>\n\n\n\n

LEP, the cloning of the ob-gene product was carried out in 199432<\/sup>.\nIt was shown that the LEP participated in regulating the body’s weight control33<\/sup>.\nLEP was regarded as a pioneering discovery because it was able to show how an\nadipose signal can be used to control the energy balance. Many of its\nactivities are related to the impacts of the brain, crossing the BBB through\nreceptor-mediated endocytosis5<\/sup> It is suspected that elevated LEP\nlevels in obese patients lead to low-grade systemic inflammation, rendering\nobese individuals more prone to CVD34<\/sup>. <\/p>\n\n\n\n

The level of\nserum LEP decreased in the groups (I, II, III), and group III decreased\nslightly more. <\/p>\n\n\n\n

Prior treatment with losartan, an angiotensin receptor type 1\nantagonist, prevented the pressor response. It was shown that blocking APN’s\naction on the metabolism of Ang III leads to a rise in its endogenous levels,\nwhich can trigger an increase in arterial blood pressure. The findings support\nthe notion that the brain RAS produces a major effector Ang III, which exerts a\ntonic control of blood pressure. The APA, which forms the brain’s Ang III is\nregarded as a potential therapeutic target35<\/sup>.<\/p>\n\n\n\n

The effects of leptin on the development of conditions such as\nstretching are known to be mediated by the increase in oxygen species. They can\nalso be triggered by the activation of the endothelin and angiotensin systems.\nOther studies suggest that the effects of leptin are mediated by the increase\nin nitric oxide production in vascular smooth muscle (VSMC). It can also impair\nthe angiotensin II’s vasoconstriction and proliferative actions36<\/sup>. ARBs would lead to a decrease in the Ang II, which leads to the expansion of\nvasodilation and limits the sympathetic neighbor’s activity, thus leading to a decrease in the level of LEP37, 38<\/sup>, the present\nstudy is consistent with the earlier studies.<\/p>\n\n\n\n

The empirical analysis of microscopical and histopathological\nappearance showed that the body-weight of the rabbit’s loads was estimated\ndaily for the four tried gatherings during the investigation period. The\nstandard load for the gatherings was diminished within 10 days and showed a non-significant slight decrease while group IV showed no difference. <\/p>\n\n\n\n

Studying the efficacy of Losartan, Telmisartan, and Candesartan on\nthe rabbit’s food consumption, the standard dietary admission showed a non-significant slight decrease while group IV showed no difference, where food admission was altogether decreased during the\nexamination time frame.<\/p>\n\n\n\n

The empirical analysis of histopathological appearance was heart,\nliver, and kidney tissues. All these changes were\nnonspecific (reactive changes). Precedent studies mentioned that specific\nheart, liver, gastrointestinal, and kidney changes were found39<\/sup>. No general specific changes that\noccur in these organs were our explanation for such a specific change. However,\nin this study, all the changes were nonspecific.<\/p>\n\n\n\n

Concerning the Correlation study of serum Ang III and LEP levels\nthe studied parameters were assessed and analyzed according to their positive\nand negative correlation coefficient with significance. The correlation of\nserum Ang III to weight, and food consumption shows a highly significant strong positive-correlation amidst\nrabbit\u2019s body-weights & food consumption post-treatment and serum Ang\nIII\nconcentrations. <\/p>\n\n\n\n

The increase in\nweight and food is through an increase in adipocytes and their synthesis.\nThese are activated by several factors, the most important of which is the RAS\nby activating the increase of the Ang II & the ACE2-Ang_(1\u20137)-Mas37, 40-42<\/sup>. The present study is consistent with previous studies in\nthat LEP does not have a significant role in regulating food and weight but\nrather is one of several factors affecting them.<\/p>\n\n\n\n

A decrease in LEP level leads to the suppression of activates STAT 3 specifically and exclusively in the hypothalamus43, 44<\/sup>. <\/p>\n\n\n\n

The correlation of serum LEP to weight, and food consumption showed a weak; non-significant\npositive -correlation amidst rabbit body-weights and food consumption post treatment & serum LEP concentrations. Also, a weak non-significant\npositive-correlation amidst serum Ang III & LEP levels in the tested groups of\nthis study. The coefficient correlation\nmay be changed to a highly significant strong positive\nif the no. of samples increases.<\/p>\n\n\n\n

The elevated levels of\nangiotensin II are influenced by the presence of renin-angiotensin-aldosterone\nsystem (RAAS) components in which the adipose tissue is its source. These\ncomponents are involved in regulating adipocyte functions. The interaction\nbetween RAAS components and adipokines has been shown to contribute to the\ndevelopment of heart failure45<\/sup>. Angiotensin II and angiotensin III\nbinding to the AT2R have effects that generally counteract its classical\nactions, producing vasodilation and Natriuresis46<\/sup>. It increases the expression and the release of proinflammatory\ncytokines37, 40-42<\/sup>, and increments LEP quality articulation and\ndischarge. Accordingly, the hindrance of Ang II by ARBs may bring about\ndecreased LEP38<\/sup>. The ARBs Losartan,\nTelmisartan, and Candesartan lowered the level of Ang III and LEP levels, as it\nlowered the level of Ang II, which suppresses the activity of the RAS that\nreduced the level of Ang III and reduced the level of adipocytes reduced the\nlevel of LEP.<\/a><\/p>\n\n\n\n

Conclusion<\/strong><\/strong><\/p>\n\n\n\n

The study’s findings show\nthat the\nserum levels of Ang III and LEP were significantly decreased in rabbits that\nwere given ARBs (Losartan, Telmisartan, or Candesartan) in comparison to baseline and controls related to the\neffects of ARBs on the levels of Ang II and the adipocytes that were shown to restrain\nthe RAS activity. The\nhistological assessment of the kidney, liver, and heart revealed that the use\nof Losartan,\nTelmisartan, or Candesartan,\nconfirmed non-specific changes in the histopathological profile. A non-significant weak positive-correlation coefficient was\nobserved between Ang\nIII & LEP. <\/p>\n\n\n\n

Future work<\/strong><\/strong><\/p>\n\n\n\n

Suggestions for this study to find out<\/p>\n\n\n\n

Assessment of the Ang III and LEP levels on large no. of animals. <\/p>\n\n\n\n

Clinical study toassess the Ang III and LEP levels in humans.<\/p>\n\n\n\n

Acknowledgment<\/strong><\/p>\n\n\n\n

The authors would like to thank Isra University. <\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

The authors disclose that there is no conflict of interest.<\/p>\n\n\n\n

Funding Sources<\/strong><\/p>\n\n\n\n

there is no funding Sources<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

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    CrossRef<\/a><\/li>
  2. Yanagawa, N., Capparelli, A.W., Jo, O.D., Friedal, A. n.n., Barrett, J.D. and Eggena, P. Production of angiotensinogen and renin-like activity by rabbit proximal tubular cells in culture. Kidney International, 1991; 39(5): pp.938\u2013941.
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