Background: Angiotensin II (Ang II) is a potent vasoconstrictor and a deleterious factor in cardiovascular pathophysiology. Ang II receptor blockers (ARBs) have recently been introduced into clinical practice for treatment of hypertension and congestive heart failure.
Aims: This study was undertaken to evaluate the inhibitory effects of ARBs on vasoconstriction in humans.
Methods: Vasomotor tone was analyzed in endothelium denuded, human coronary artery (HCA) segments. Ang II type 1 (AT(1)) and type 2 (AT(2)) receptor mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR).
Results: Ang II was a potent vasoconstrictor (pEC(50) = 7.7). At 1 nM of the AT(1) receptor antagonists, candesartan and valsartan, the maximum contraction was depressed to 57 and 50% of Ang II, respectively, indicating insurmountability. Although generally considered surmountable, the presence of 100 nM losartan elicited a depression of the Ang II response to 32%. Its active metabolite, EXP 3174 (1 nM), abolished the Ang II contraction. The AT(1) receptor antagonists had the following order of blocking effect; EXP 3174 > candesartan = valsartan > losartan. The AT(2) receptor antagonist, PD 123319 (100 nM) significantly attenuated the Ang II contraction (E(max) = 62% of Ang II). RT-PCR of HCA smooth muscle cells demonstrated expression of both AT(1) and AT(2) receptor mRNA.
Conclusions: Ang II contraction in HCA is mediated mainly by AT(1) but also involves AT(2) receptors. The active metabolite of losartan, EXP 3174, is the most efficacious AT(1) receptor antagonist in HCA.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s1388-9842(02)00166-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophages.
Cell Rep
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, China. Electronic address:
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by excess accumulation of the extracellular matrix (ECM). The role of macrophage-fibroblast crosstalk in lung fibrogenesis is incompletely understood. Here we found that fibroblast growth factor-inducible molecule 14 (Fn14), the receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is highly induced in myofibroblasts in the lungs of IPF patients and the bleomycin-induced lung fibrosis model.
View Article and Find Full Text PDFHypertension: A Continuing Public Healthcare Issue.
Int J Mol Sci
December 2024
Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Hypertension is a cardiovascular disease defined by an elevated systemic blood pressure. This devastating disease afflicts 30-40% of the adult population worldwide. The disease burden for hypertension is great, and it greatly increases the risk of cardiovascular morbidity and mortality.
View Article and Find Full Text PDFPGE and HCN2 ion channels are critical mediators of pain initiated by angiotensin II.
Brain Behav Immun
December 2024
Wolfson Sensory, Pain and Regeneration Centre, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK. Electronic address:
Angiotensin II is well known to have an important influence on blood pressure, mediated via the angiotensin II type 1 receptor (AT1R), but more recent studies have shown that angiotensin II may play an important additional role in eliciting pain via a distinct action at the angiotensin II type 2 receptor (AT2R). Signalling pathways that link activation of AT2R to a sensation of pain are, however, incompletely understood. Here we use rodent inflammatory pain models to confirm that selective activation of AT2R triggers aversive responses, and that these are abolished by either antagonism or genetic deletion of AT2R.
View Article and Find Full Text PDFMelatonin attenuates responses to angiotensin II in isolated aortic rings of STZ-induced type 1-like DM rats.
Endocr Res
December 2024
Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq.
Background: In patients with diabetes mellitus (DM), vascular endothelial dysfunction (VED) is the main reason for impaired life expectancy. Melatonin (MEL) demonstrates wide-ranging effects across various organs and exhibits pleiotropic characteristics. The current study aims to investigate the modulatory roles of MEL vascular response to angiotensin II (Ang II) and its receptors including angiotensin type 1 receptor (AT-1 R) and angiotensin type 2 receptor (AT-2 R) in isolated thoracic aorta of non-diabetes (non-DM) and diabetes (DM) rats.
View Article and Find Full Text PDFFasting recovers age-related hypertension in the rats: reset of renal renin-angiotensin system components and klotho.
BMC Nephrol
December 2024
Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Article Synopsis
- The study examined how intermittent fasting impacts age-related high blood pressure and the renal renin-angiotensin system in rats.
- Older rats showed higher blood pressure and hormone levels associated with hypertension compared to younger rats, as well as lower levels of α-klotho and kidney receptor proteins.
- Intermittent fasting, especially every other day fasting, effectively lowered blood pressure and improved certain RAS components in older rats, indicating its potential benefits for managing age-related hypertension.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!