جستجوی مقالات مرتبط با کلیدواژه « angiotensin 1-7 » در نشریات گروه « پزشکی »

The sympathetic nervous system and the renin-angiotensin system (RAS) are the most pivotal vasoactive systems in regulating renal hemodynamics. The main objective of this study was to determine the role of the angiotensin II (Ang II) type 1 receptor (AT1R) antagonist on renal hemodynamic responses to Ang 1-7 infusion in innervated and denervated male and female rats.

Male and female Wistar rats underwent unilateral nephrectomy. Four weeks later, they were divided into two groups: innervated and acutely denervated groups. Subsequently, the anesthetized and catheterized rats in both groups were treated with saline as a vehicle and losartan infusion. Mean arterial pressure (MAP), renal blood flow (RBF), renal perfusion pressure (RPP), and renal vascular resistance (RVR) responses to Ang 1-7 (100, 300, and 1000 ng kg−1 min−1 ) were then measured at controlled RPP.

Basal MAP, RPP, RBF, and RVR did not show significant differences between the intact and denervated groups. Losartan significantly decreased MAP, RPP, and RVR in both innervated and denervated male and female rats (P<0.001), while RBF increased only in innervated and denervated female rats (P<0.004). However, following Ang 1-7 administration, the RBF response to Ang 1-7 infusion differed significantly between intact and denervated male rats treated with losartan (P<0.04). This response was not observed in female rats.

These data suggest a synergistic effect of losartan and Ang 1-7 on increased RBF in the presence of renal sympathetic nerves in male rats.

The renin–angiotensin system (RAS) exerts profound physiological effects on blood pressure regulation and fluid homeostasis, mainly by modulating renal, cardiovascular, and central nervous systems. Angiotensin (Ang)-(1-7), an end-product of RAS, is recognized by its cardiovascular protective properties through stimulation of the Mas receptor, including vasodilation, anti-inflammatory, and antihypertensive actions, and consequently, counter-regulating the well-known Ang II-elicited actions. The overall hypothesis of this study is that Ang-(1-7) inhibits Ang II-induced ERK1/2 activation in vascular smooth muscle cells (VSMCs), via regulation of mitogen-activated protein phosphatase-1 (MKP-1) activity. Aortas from male Wistar rats were incubated with Ang-(1-7) or vehicle. Concentration-response curves to Ang II were performed in endothelium-denuded aortas, in the presence or absence of ERK1/2 (PD98059) inhibitor or Mas receptor (A-779) antagonist. Expression of proteins was assessed by western blot, and immunohistochemistry was conducted in VSMCs. Ang-(1-7) incubation decreased Ang II-induced contractile response in aortas, and this effect was not observed in the presence of PD98059 or A-779. Stimulation of VSMCs with Ang-(1-7) prevented Ang II-induced ERK1/2 phosphorylation, but not C-Raf-activation. Furthermore, Ang II decreased MKP-1 phosphorylation in VSMCs. Interestingly, simultaneous incubation of Ang-(1-7) with Ang II favored MKP-1 phosphorylation, negatively modulating ERK1/2 activation in VSMCs. The results suggest that Ang-(1-7) counter-regulates actions evoked by Ang II overproduction, as observed in cardiovascular diseases, mainly by modulating MKP-1 activity. This evidence suggests that the role of Ang-(1-7) in MKP-1-regulation represents a target for new therapeutic development.

Ischemia/reperfusion (I/R) is a major cause of acute kidney injury. Several studies have shown that renin angiotensin (Ang) system and activation of Ang II type 1 receptor (AT1) are involved in various forms of kidney diseases. Likewise, Ang 1-7 as a physiologic antagonist of AT1 and losartan could possibly protect the kidney against I/R damage. Therefore, we investigated renal injury by administering the drugs before and after I/R. </strong>Fifty-four male Wistar rats were randomly assigned to five groups as follows. 1, Sham operated; 2, saline group (as a control group); 3, losartan group; 4, Ang 1-7group; and 5, Ang 1-7 + losartan simultaneously. It should be noted that groups 2-5 consisted of two separate I/R-induced subgroups both receiving medication where the first groups received the treatment 15 min before induction of I/R while the medications were given to the second groups immediately after induction of I/R. Twenty four h after I/R, blood samples were collected, and then levels of serum urea nitrogen (BUN), creatinine (Cr), nitrite, malondialdehyde (MDA), lactate dehydrogenase (LDH) and total antioxidant capacity (TAC) were measured. Likewise, nitrite, MDA and TAC were measured in the homogenized kidney tissues. After the induction of I/R, the BUN, Cr, LDH, and kidney tissue damage score increased. Administration of Ang 1-7 alone or simultaneously with losartan decreased the levels of aforementioned factors. Also,kidney MDA and nitrate levels significantly increased after I/R induction (P</em> < 0.05). According to the results of this study, it can be claimed that the effect of losartan in the presence of Mas receptor is statistically significant and kidney damage dramatically decreases.

Renin-angiotensin system (RAS) plays an important role in cardiovascular and kidney functions to regulate the systematic blood pressure. The baroreflex sensitivity (BRS) index is a quantitative index that was considered as a prognostic indicator for cardiovascular system risk which is known as heart rate change to blood pressure change ratio ( HR MAP ∆ ∆ ). Sympathetic nerve is an arm of the BRS which may be influenced by RAS vasodilatory arm function.
To determine the role of angiotensin 1-7 (Ang1-7) accompanied by bilateral renal denervation (RDN) on BRS and renal function.
Male and female anesthetized Wistar rats were subjected to RDN and treated with Ang1-7 (300 and 1000 ng.kg-1.min-1). Mean arterial pressure (MAP) and heart rate (HR) responses to phenylephrine (PE) infusion were measured to determine BRS index. As kidney function markers, the creatinine clearance (CrCl) and urine flow (UF) were also determined.
The results showed that BRS increased significantly in RDN male rats treated with Ang1-7 compared to vehicle (P The Ang1-7 infusion could alter the BRS index in RDN rat’s gender dependently. The ClCr response to Ang1-7 infusion in male rats was dose related.

The angiotensin 1-7 (Ang1-7) Mas receptor (MasR) axis, bradykinin (BK) and female sex hormone are involved in releasing of vasodilatory biomarkers including Nitric Oxide (NO). We examined the role of MasR and BK on NO metabolite (nitrite) production response to Ang 1-7 infusion in ovariectomized rats treated with estradiol.
A total of 48 female Wistar rats were divided into 2 main groups; ovariectomized treated with placebo (OVX) and ovariectomized treated with estradiol valerate (OVE) for period of two weeks. Then after anesthetization, the animals of each groups were divided into four subgroups that received MasR antagonist (A779) or , BK, BKξ or vehicle, and they were subjected to Ang1-7 infusion (0, 100, 300 and 1000 ng/kg/min). The level of nitrite (NO metabolite) was measured by Griess method.
The serum level of nitrite response to Ang 1-7 administration in OVE group was incrased when compared with OVX group, however when MasR was blocked by A799, the increased nitrite level was abolished. BK also increased the level of nitrite but co administration of BK and A779 did not enhance the nitrite level in both OVE and OVX groups.
Estradiol and Bk increase nitrite production in response to Ang 1-7 infusion in condition of MasR presence.

Unilateral ureteral obstruction (UUO) is a clinical scenario that leads to obstructive nephropathy. UUO alters the expression of many mediators in the ipsilateral kidney. Renin-angiotensin system (RAS) is involved in UUO. Angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7) as the main arms of RAS influence kidney function which may alter by UUO. Ang II via Ang II receptor subtypes I (AT1R) reduces renal blood flow and glomerular filtration rate and induces oxidative stress, apoptosis as well as inflammation in renal tissue and contributes to renal fibrosis in UUO model. Also, Ang 1-7 receptor (MasR) and Ang II receptor subtype II (AT2R) may have a protective effect against UUO-induced renal injury. In addition, there is crosstalk among RAS with the main vasodilator factors (prostaglandins E2 and I2, bradykinin, atrial natriuretic factor, nitric oxide and adenosine) and the main vasoconstrictor factors (endothelin and vasopressin) in the ipsilateral kidney with UUO. In this review, the roles of the RAS on renal function and its interactions with the other factors in the kidney with UUO were discussed.