Effects of chronic treatment with Iosartan on blood pressure, endothelin-like immunoreactivity and nitric oxide in normotensive rats

Sacerdote, A; Cosenzi, Alessandro; Bocin, Elena; Molino, Rossella; Seculin, Paolo; Plazzotta, N.; Luxich, Elena; Bellini, Giuseppe

doi:10.1097/00004872-199512010-00029

Cited by 4 publications

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“…Losartan is an antihypertensive drug that binds to the angiotensin II receptors of endothelial cells, preventing them from releasing endothelins. Endothelins are powerful vasoconstrictors; therefore, losartan ultimately inhibits vasoconstriction, lowering blood pressure. , Besides its effects on blood pressure, a research group led by Jain showed that losartan could reduce the production of two primary components of the tumor extracellular matrix that are often associated with blood vessel compression and low tumor vascular perfusion, namely, collagen and hyaluronan . By harnessing of its effects on tumor extracellular matrix, losartan could thus be used to improve drug delivery to tumors.…”

Section: Resultsmentioning

confidence: 99%

Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study

et al. 2020

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Delivery efficiencies of theranostic nanoparticles (NPs) based on passive tumor targeting strongly depend either on their blood circulation time or on appropriate modulations of the tumor microenvironment. Therefore, predicting the NP delivery efficiency before and after a tumor microenvironment modulation is highly desirable. Here, we present a new erythrocyte membranecamouflaged magnetofluorescent nanocarrier (MMFn) with long blood circulation time (92 h) and high delivery efficiency (10% ID for Ehrlich murine tumor model). MMFns owe their magnetic and fluorescent properties to the incorporation of manganese ferrite nanoparticles (MnFe 2 O 4 NPs) and IR-780 (a lipophilic indocyanine fluorescent dye), respectively, to their erythrocyte membrane-derived camouflage. MMFn composition, morphology, and size, as well as optical absorption, zeta potential, and fluorescent, magnetic, and magnetothermal properties, are thoroughly examined in vitro. We then present an analytical pharmacokinetic (PK) model capable of predicting the delivery efficiency (DE) and the time of peak tumor uptake (t max ), as well as changes in DE and t max due to modulations of the tumor microenvironment, for potentially any nanocarrier. Experimental PK data sets (blood and tumor amounts of MMFns) are simultaneously fit to the model equations using the PK modeling software Monolix. We then validate our model analytical solutions with the numerical solutions provided by Monolix. We also demonstrate how our a priori nonmechanistic model for passive targeting relates to a previously reported mechanistic model for active targeting. All in vivo PK studies, as well as in vivo and ex vivo biodistribution studies, were conducted using two noninvasive techniques, namely, fluorescence molecular tomography (FMT) and alternating current biosusceptometry (ACB). Finally, histopathology corroborates our PK and biodistribution results.

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Section: Resultsmentioning

confidence: 99%

Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study

et al. 2020

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“…Nevertheless, our results are in line with previous evidence that CVS does not affect HR ( Cudnoch-Jedrzejewska et al, 2010 ; Flak et al, 2011 ; Xie et al, 2012 ; Almeida et al, 2015 ). It has been demonstrated that chronic treatment with losartan at doses ranging from 10 to 40 mg/kg decreased the basal arterial pressure in normotensive rats ( Sacerdote et al, 1995 ; Bezerra et al, 2001 ; Leenen et al, 2001 ; Xavier et al, 2004 ; Koprdova et al, 2009 ). This is in accordance with our results.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Type 1 Angiontensin II Receptor (AT1) in Cardiovascular Changes Induced by Chronic Emotional Stress: Comparison between Homotypic and Heterotypic Stressors

et al. 2016

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Consistent evidence has shown an important role of emotional stress in pathogenesis of cardiovascular diseases. Additionally, studies in animal models have demonstrated that daily exposure to different stressor (heterotypic stressor) evokes more severe changes than those resulting from repeated exposure to the same aversive stimulus (homotypic stressor), possibly due to the habituation process upon repeated exposure to the same stressor. Despite these pieces of evidence, the mechanisms involved in the stress-evoked cardiovascular dysfunction are poorly understood. Therefore, the present study investigated the involvement of angiotensin II (Ang II) acting on the type 1 Ang II receptor (AT1) in the cardiovascular dysfunctions evoked by both homotypic and heterotypic chronic emotional stresses in rats. For this purpose, we compared the effect of the chronic treatment with the AT1 receptor antagonist losartan (30 mg/kg/day, p.o.) on the cardiovascular and autonomic changes evoked by the heterotypic stressor chronic variable stress (CVS) and the homotypic stressor repeated restraint stress (RRS). RRS increased the sympathetic tone to the heart and decreased the cardiac parasympathetic activity, whereas CVS decreased the cardiac parasympathetic activity. Additionally, both stressors impaired the baroreflex function. Alterations in the autonomic activity and the baroreflex impairment were inhibited by losartan treatment. Additionally, CVS reduced the body weight and increased the circulating corticosterone; however, these effects were not affected by losartan. In conclusion, these findings indicate the involvement of angiotensin II/AT1 receptors in the autonomic changes evoked by both homotypic and heterotypic chronic stressors. Moreover, the present results provide evidence that the increase in the circulating corticosterone and body weight reduction evoked by heterotypic stressors are independent of AT1 receptors.

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OBESE FEMALE SHHF/Mcc-fa^cpRATS RESIST ANTIHYPERTENSIVE EFFECTS OF RENIN-ANGIOTENSIN SYSTEM INHIBITION

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Holycross

McCune

et al. 2001

Clinical and Experimental Hypertension

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Gender and obesity may influence response to pharmacological modulation of the renin-angiotensin system. We used SHHF/Mcc-fa(cp) rats to study effect of obesity and gender on the ability of an AT1 receptor antagonist to decrease blood pressure. After 2 weeks treatment with irbesartan (50 mg/kg), only lean and obese males showed significant decreases in blood pressure, while obese females were completely resistant. Lean females showed a trend toward lowering of pressure (p=0.06). However, irbesartan similarly shifted angiotensin II dose response curves to the right in all groups. Twelve weeks of irbesartan also failed to decrease blood pressure, but did significantly reduce heart weight in obese females. In untreated rats, obese females had lower plasma renin activity and serum angiotensin converting enzyme activity compared to lean males, while lean and obese females had increased urinary endothelin excretion. Despite an otherwise similar genetic background contributing to hypertension and heart failure, obese females have different patterns of humoral activation compared to lean males, which may contribute to their resistance to the depressor effects of irbesartan.

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Effects of chronic treatment with Iosartan on blood pressure, endothelin-like immunoreactivity and nitric oxide in normotensive rats

Cited by 4 publications

References 0 publications

Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study

Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study

Involvement of Type 1 Angiontensin II Receptor (AT1) in Cardiovascular Changes Induced by Chronic Emotional Stress: Comparison between Homotypic and Heterotypic Stressors

OBESE FEMALE SHHF/Mcc-fa^cpRATS RESIST ANTIHYPERTENSIVE EFFECTS OF RENIN-ANGIOTENSIN SYSTEM INHIBITION

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Effects of chronic treatment with Iosartan on blood pressure, endothelin-like immunoreactivity and nitric oxide in normotensive rats

Cited by 4 publications

References 0 publications

Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study

Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study

Involvement of Type 1 Angiontensin II Receptor (AT1) in Cardiovascular Changes Induced by Chronic Emotional Stress: Comparison between Homotypic and Heterotypic Stressors

OBESE FEMALE SHHF/Mcc-facpRATS RESIST ANTIHYPERTENSIVE EFFECTS OF RENIN-ANGIOTENSIN SYSTEM INHIBITION

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OBESE FEMALE SHHF/Mcc-fa^cpRATS RESIST ANTIHYPERTENSIVE EFFECTS OF RENIN-ANGIOTENSIN SYSTEM INHIBITION