The classically recognized functions of the renin-angiotensin system are mediated by type 1 (AT1) angiotensin receptors. Whereas man possesses a single AT1 receptor, there are two AT1 receptor isoforms in rodents (AT1A and AT1B) that are products of separate genes (Agtr1a and Agtr1b). We have generated mice lacking AT1B (Agtr1b -/-) and both AT1A and AT1B receptors (Agtr1a -/-Agtr1b -/-). Agtr1...

Methods In this study we examined the possible functional consequence of transactivation within angiotensin AT1 receptor homodimers. To do this, we used the S109Y mutant of the AT1 receptor, in which the binding site of the nonpeptid AT1 receptor antagonist, candesartan, was destroyed. Expressing this mutant receptor together with the wildtype in CHO cells, in the presence of candesartan, we co...

Response to Lack of Specificity of Commercial Antibodies Leads to Misidentification of Angiotensin Type-1 Receptor Protein We read with great interest the letter from Eguchi et al1 providing additional evidence to support the lack of suitability of commercial antibodies for detecting angiotensin type-1 (AT1) receptor protein in experimental systems. The data from Eguchi and associates extend ou...

Hyperactivity of the renin-angiotensin-aldosterone system through the angiotensin II (Ang II)/Ang II type 1 receptor (AT1-R) axis constitutes a hallmark of hypertension. Recent findings indicate that only a subset of AT1-R signaling pathways is cardiodeleterious, and their selective inhibition by biased ligands promotes therapeutic benefit. To date, only synthetic biased ligands have been descr...

AIMS We recently demonstrated that aldosterone induces a non-genomic vasoconstrictor effect on rat coronary arterioles and that this effect was blocked by angiotensin II type 1 receptor (AT1) blockers. Intracellular transglutaminase enhances AT1 signalling by cross-linking AT1 homodimers. The purpose of this study was to confirm the AT1-dependency of the vasoconstrictor effect of aldosterone us...

OBJECTIVE To examine the exact profile of expression and to determine the functional significance of the angiotensin II (Ang II), type I (AT1) and type 2 (AT2) receptors during rat aortic development and following rat carotid artery balloon injury. METHODS AT1 and AT2 mRNA levels in rat aortae were measured using a quantitative reverse transcription polymerase chain reaction technique. Ang II...

Preeclampsia is a life-threatening pregnancy disorder that is widely thought to be triggered by impaired placental development. However, the placenta-related pathogenic factors are not fully identified, and their underlying mechanisms in disease development remain unclear. Here, we report that the protein level and enzyme activity of tissue transglutaminase (TG2 or tTG), the most ubiquitous mem...

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), ...

Caveolae are membrane domains that have been implicated in signal transduction, and caveolins are major structural components of these domains. We found that all reported caveolin isoforms (caveolin-1, -2, and -3) were expressed in vascular smooth muscle cells (VSMCs); however, only caveolin-1 mRNA was regulated by angiotensin II (Ang II). Ang II (100 nmol/L) increased caveolin-1 mRNA, with a p...

Angiotensin II (Ang II) type 1 (AT1) receptor is known to mediate a variety of physiological actions of Ang II including autophagy. However, the role of AT1 receptor in cardiomyocyte autophagy triggered by mechanical stress still remains elusive. The aim of this study was therefore to examine whether and how AT1 receptor participates in cardiomyocyte autophagy induced by mechanical stresses. A ...