Retinal vascular reactivity to norepinephrine and angiotensin II in normals and diabetics

Background The cardiovascular protective effects of estrogens in premenopausal women depend mainly on estrogen receptor α (ERα). ERα activates nuclear gene transcription regulation and membrane‐initiated signaling. The latter plays a key role in estrogen‐dependent activation of endothelial NO synthase. The goal of the present work was to determine the respective roles of the 2 ERα activities in endothelial function and cardiac and kidney damage in young and old female mice with hypertension, which is a major risk factor in postmenopausal women. Methods and Results Five‐ and 18‐month‐old female mice lacking either ERα (ERα −/− ), the nuclear activating function AF2 of ERα (AF2°), or membrane‐located ERα (C451A) were treated with angiotensin II (0.5 mg/kg per day) for 1 month. Systolic blood pressure, left ventricle weight, vascular reactivity, and kidney function were then assessed. Angiotensin II increased systolic blood pressure, ventricle weight, and vascular contractility in ERα −/− and AF2° mice more than in wild‐type and C451A mice, independent of age. In both the aorta and mesenteric resistance arteries, angiotensin II and aging reduced endothelium‐dependent relaxation in all groups, but this effect was more pronounced in ERα −/− and AF2° than in the wild‐type and C451A mice. Kidney inflammation and oxidative stress, as well as blood urea and creatinine levels, were also more pronounced in old hypertensive ERα −/− and AF2° than in old hypertensive wild‐type and C451A mice. Conclusions The nuclear ERα‐AF2 dependent function attenuates angiotensin II–dependent hypertension and protects target organs in aging mice, whereas membrane ERα signaling does not seem to play a role.

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Hypertension in insulin-resistant Zucker obese rats is independent of sympathetic neural support

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.262.3.e368 ◽

1992 ◽

Vol 262 (3) ◽

pp. E368-E371 ◽

Cited By ~ 7

Author(s):

M. B. Zemel ◽

J. D. Peuler ◽

J. R. Sowers ◽

L. Simpson

Keyword(s):

Angiotensin Ii ◽

Neural Activity ◽

Vascular Reactivity ◽

Zucker Rats ◽

Ganglionic Blockade ◽

Intravenous Injections ◽

Insulin Resistant ◽

Arterial Blood ◽

Obese Rats ◽

Blood Pressure Responses

We have previously reported that insulin-resistant Zucker obese rats exhibit hypertension associated with impaired vascular smooth muscle (VSM) Ca2+ transport and proposed that this results from failure of insulin to regulate VSM Ca2+ transport in insulin resistance. However, hypertension in insulin-resistant states is generally attributed to hyperinsulinemia, with a consequent stimulation of sympathetic neural activity. Accordingly, the present study was conducted to determine whether the hypertension observed in Zucker obese rats compared with their lean controls was dependent on either increased sympathetic neural activity or exaggerated vascular reactivity. Intra-arterial blood pressure responses to ganglionic blockade with Ecolid (chlorisondamine chloride) and to graded intravenous injections of angiotensin II and norepinephrine were compared in 6- to 8-wk-old male Zucker rats and their lean controls (n = 10/group). The obese rats exhibited significant hypertension before ganglionic blockade (P less than 0.001), and this difference was largely sustained during ganglionic blockade (P less than 0.005). Furthermore, the obese rats exhibited greater pressor sensitivity to both angiotensin II and to norepinephrine during ganglionic blockade (P less than 0.01). Thus enhanced pressor sensitivity, independent of sympathetic neural activity, appears to support hypertension in Zucker obese rats.

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Total autonomic blockade eliminates the attenuated pressor response to angiotensin II in pregnant rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.265.6.r1270 ◽

1993 ◽

Vol 265 (6) ◽

pp. R1270-R1275

Author(s):

T. Hines ◽

M. D. Lindheimer ◽

W. M. Barron

Keyword(s):

Angiotensin Ii ◽

Repeated Measures ◽

Vascular Reactivity ◽

Peripheral Resistance ◽

Systemic Resistance ◽

Bolus Administration ◽

Ang Ii ◽

Pregnant Rats ◽

Pressor Responses ◽

Autonomic Blockade

Pressor responses to angiotensin II (ANG II) are markedly attenuated in reflex-intact pregnant animals, a phenomenon widely attributed to intrinsic changes in vascular reactivity. To test the hypothesis that gestational augmentation of neural reflex activity contributes importantly to this phenomenon, changes in mean arterial pressure (MAP), cardiac output (CO), and total peripheral resistance (TPR) were compared during constant infusion (25-400 ng.kg-1.min-1) of ANG II in conscious virgin and pregnant rats, using a model of total autonomic blockade (chlorisondamine chloride and methscopolamine bromide), with restoration of baseline hemodynamics by infusion of norepinephrine. Basal CO was higher and TPR lower in pregnant (CO 121.8 +/- 3.8 ml/min; TPR 0.78 +/- 0.04 mmHg.ml-1.min) compared with virgin (CO 95.9 +/- 3.9 ml/min; TPR 1.05 +/- 0.08 mmHg.ml-1.min) rats (P < 0.005). Pressor responses to ANG II were similar in both groups of reflex-blocked animals due to comparable changes in TPR and CO (not significant by repeated-measures analysis of variance). Other experiments demonstrated that changes in MAP after bolus administration of ANG II did not differ in areflexic virgin and gravid rats. Thus in the absence of autonomic control ANG II has similar effects on systemic resistance in pregnant and nonpregnant rats, suggesting that reflex neural mechanisms contribute significantly to gestational changes in pressor responsiveness. These data further suggest that pregnancy is not accompanied by a generalized decrease in vascular reactivity to all pressor agents.

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Early Morphofunctional Changes in AngII-Infused Mice Contribute to Regional Onset of Aortic Aneurysm and Dissection

Journal of Vascular Research ◽

10.1159/000509545 ◽

2020 ◽

Vol 57 (6) ◽

pp. 367-375

Author(s):

Lydia Aslanidou ◽

Bram Trachet ◽

Linda Sasset ◽

Goran Lovric ◽

Nikolaos Stergiopulos ◽

...

Keyword(s):

Angiotensin Ii ◽

Aortic Aneurysm ◽

Abdominal Aorta ◽

Vascular Reactivity ◽

Ex Vivo ◽

Aortic Aneurysms ◽

Microstructural Damage ◽

Suprarenal Aorta ◽

Aortic Aneurysm And Dissection

Aortic aneurysms and dissections are silent and lethal conditions, whose pathogenesis remains incompletely understood. Although angiotensin II (AngII)-infused ApoE−/− mice have been widely used to study aortic aneurysm and dissection, early morphofunctional alterations preceding the onset of these conditions remain unknown. The goal of this study was to unveil early morphofunctional changes underlying the onset of aneurysm and dissection. At 3 days post-AngII infusion, suprarenal abdominal aorta presented significant volumetric dilatation and microstructural damage. Ex vivo assessment of vascular reactivity of the suprarenal dissection-prone aorta and its side branches, showed an endothelial and contractile dysfunctions that were severe in the suprarenal aorta, moderate distally, and absent in the side branches, mirroring the susceptibility to dissection of these different vascular segments. Early and specific morphofunctional changes of the suprarenal aorta may contribute to the regional onset of aortic aneurysm and dissection by exacerbating the biomechanical burden arising from its side branches.

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Physiological and Biochemical Vascular Reactivity Parameters of Angiotensin II and the Action of Biased Agonist TRV023

Advances in Pharmacological and Pharmaceutical Sciences ◽

10.1155/2020/3092721 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Marcos André Soares Leal ◽

Thanisia de Almeida ◽

João Guilherme Torres ◽

Luciene Cristina Gastalho Campos ◽

Elisardo Corral Vasquez ◽

...

Keyword(s):

Angiotensin Ii ◽

Vascular Reactivity ◽

Renin Angiotensin System ◽

Aortic Ring ◽

Experimental Models ◽

Organ Bath ◽

Angiotensin System ◽

Active Peptides ◽

Pharmacological Studies ◽

Physiological And Biochemical

Vascular reactivity experiments using isolated aortic rings have been widely used as a model for physiological and pharmacological studies since the early sixties. Here, we suggest several parameters that the researcher should pay attention to when investigating angiotensin II in their experimental models. Angiotensin II is one of the active peptides of the renin-angiotensin system and exerts its effect through the AT1 and AT2 receptors. Some studies seek to understand the effects of angiotensin II receptors at the vascular level by using vascular reactivity experiments. However, because of the large number of variations, there are only a handful of reactivity studies that seek to use this method. Thus, the objective of this study was to standardize experimental methods with angiotensin II, through vascular reactivity protocols. For this, variables such as basal tension, concentration interval, single concentration, curve concentration response, and multiple experiments using the same aortic ring were developed using the technique of vascular reactivity in an organ bath. This is the first study that has standardized the vascular reactivity protocol. In addition, we demonstrated the effects of TRV023-biased ligand of the AT1R at vascular sites.

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