AngII AT2 receptor modulates AT1 mediated descending vasa recta endothelial Ca2+ signaling. We tested whether the respective AT1 and AT2 receptor subtype antagonists, losartan and PD123319 could block the descending vasa recta (DVR) endothelial intracellular calcium ([Ca]i) suppression induced by AngII. AngII partially reversed the increase in [Ca]i generated by cyclopiazonic acid (CPA, 10 M), ...

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This study assesses the receptor subtype (AT1 and AT2) through which angiotensin II (Ang II) mediates contraction in small arteries of young and adult spontaneously hypertensive rats (SHR). Segments of third-order mesenteric arteries ( approximately 200 microm in lumen diameter) were mounted in a pressurized system. Systolic blood pressure and media:lumen ratio of small arteries were significan...

The human angiotensin II type 1 (AT1) receptor gene was isolated and its promoter function analyzed by deletion mutant promoter/luciferase constructs in transfected Cos 7 cells. We found that epidermal growth factor enhanced the human AT1 promoter activity twofold to threefold. The region between -227 and -366 bp from the 5' end of the cDNA was mapped for a base sequence responsive to the epide...

Disruption of angiotensin II type 1 (AT1) receptor prolonged life span in mice. Since aging-related decline in skeletal muscle function was retarded in Atgr1a(-/-) mice, we examined the role of AT1 receptor in muscle regeneration after injury. Administration of AT1 receptor blocker irbesartan increased the size of regenerating myofibers, decreased fibrosis, and enhanced functional muscle recove...

The evolving complexity associated with the renin-angiotensin cascade has been the focus of increasingly sophisticated pharmacological experimentation. The identification of at least 2 angiotensin II (Ang II) receptor subtypes led to functional subclassification of their activity. Activation of the type 1 (AT1) receptor is associated with the vasopressive and aldosterone-secreting effects of An...

This study investigated the process of nitric oxide (NO) release from platelets after stimulation with different angiotensin II type 1 (AT1)-receptor antagonists and its effect on platelet adhesion and aggregation. Angiotensin II AT1-receptor antagonist-stimulated NO release in platelets was compared with that in human umbilical vein endothelial cells by using a highly sensitive porphyrinic mic...

Patients with hypertension often manifest a dysregulated renin-angiotensinaldosterone system (RAAS). Most of the available treatment approaches for hypertension are targeted towards the RAAS including direct renin inhibition, ACE inhibition, angiotensin II type 1 receptor (AT1-R) blockade, and aldosterone receptor antagonism. The Jak2 signaling pathway is intricately coupled to the AT1-R signal...

The endothelial lining of the blood-brain barrier tightly controls the distribution of peptide hormones between the central nervous system and the circulation. By using primary cultures of brain microvessel endothelial cells, an in vitro model of the blood-brain barrier, we report here the uptake and transport of the octapeptide angiotensin II by a specific receptor population. With the angiote...

Angiotensin II exerts its physiological effects by activating multiple subtypes of its receptor such as AT1a-, AT1b-, and AT2-receptors. Because of a high degree of similarity among these G-protein-coupled receptors, it has been difficult to assign diverse physiological actions of angiotensin II through these receptor subtypes. We have developed small interfering RNAs to selectively inhibit the...