Sartans are non-peptide AT(1) receptor antagonists used to treat hypertension and related pathologies. Their effects on the G protein-dependent responses of angiotensin II (Ang II) were the same in vascular tissues and in isolated cell systems. All are competitive but, when pre-incubated, they act surmountably (only rightward shift of the Ang II concentration-response curve) or insurmountably (also decreasing the maximal response). Insurmountable behaviour reflects the formation of tight sartan-receptor complexes; it is often partial due to the co-existence of tight and loose complexes. Their ratio positively correlates with the dissociation half-life of the tight complexes and depends on the sartan: i.e. candesartan>olmesartan>telmisartan approximately equal EXP3174>valsartan>irbesartan>losartan. When AT(1) receptors display sufficient basal activity (in case of receptor over-expression, mutation and, especially, tissue stretching) sartans may also act as inverse agonists. This rather affects long-term, G protein-independent hypertrophic responses leading to cardiovascular remodelling.
Mechanical stress activates protein kinase cascade of phosphorylation in neonatal rat cardiac myocytes
BMS-180560, an insurmountable inhibitor of angiotensin II-stimulated responses: comparison with losartan and EXP3174
Pharmacological characterization of the novel nonpeptide angiotensin II receptor antagonist, BIBR 277
Pharmacological profile of valsartan: a potent, orally active, nonpeptide antagonist of the angiotensin II AT1-receptor subtype
Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro
Mutation of Asn111 in the third transmembrane domain of the AT1A angiotensin II receptor induces its constitutive activation.
In vitro pharmacological characterization of a new selective angiotensin AT1 receptor antagonist, UR-7280
The conformational change responsible for AT1 receptor activation is dependent upon two juxtaposed asparagine residues on transmembrane helices III and VII.
Mechanical stretch/relaxation stimulates a cellular renin-angiotensin system in cultured rat mesangial cells
Mechanical stretch induces hypertrophic responses in cardiac myocytes of angiotensin II type 1a receptor knockout mice.
Cultured neonatal rat cardiac myocytes and fibroblasts do not synthesize renin or angiotensinogen: evidence for stretch-induced cardiomyocyte hypertrophy independent of angiotensin II
Systematic identification of mutations that constitutively activate the angiotensin II type 1A receptor by screening a randomly mutated cDNA library with an original pharmacological bioassay
A two-state receptor model for the interaction between angiotensin II type 1 receptors and non-peptide antagonists
Interaction between the partially insurmountable antagonist valsartan and human recombinant angiotensin II type 1 receptors
Lys(199) mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists
Connective tissue growth factor mRNA expression pattern in cartilages is associated with their type I collagen expression
Effect of reduced angiotensin-converting enzyme gene expression and angiotensin-converting enzyme inhibition on angiotensin and bradykinin peptide levels in mice
Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II
Novel mechanisms of valsartan on the treatment of acute myocardial infarction through inhibition of the antiadhesion molecule periostin
Kinetic versus allosteric mechanisms to explain insurmountable antagonism and delayed ligand dissociation
Differential bonding interactions of inverse agonists of angiotensin II type 1 receptor in stabilizing the inactive state.
Structure-kinetic relationships--an overlooked parameter in hit-to-lead optimization: a case of cyclopentylamines as chemokine receptor 2 antagonists
Cross-coupling of diarylborinic acids and anhydrides with arylhalides catalyzed by a phosphite/N-heterocyclic carbene co-supported palladium catalyst system
Multivalent ligand-receptor interactions elicit inverse agonist activity of AT(1) receptor blockers against stretch-induced AT(1) receptor activation
Comparison of angiotensin II type 1-receptor blockers to regress pressure overload-induced cardiac hypertrophy in mice
Sympathoinhibition caused by orally administered telmisartan through inhibition of the AT₁ receptor in the rostral ventrolateral medulla of hypertensive rats
Effects of losartan vs candesartan in reducing cardiovascular events in the primary treatment of hypertension.
Sympathoinhibitory effects of telmisartan through the reduction of oxidative stress in the rostral ventrolateral medulla of obesity-induced hypertensive rats
Effects of the angiotensin II receptor blocker losartan on the monocyte expression of biglycan in hypertensive patients
Abilities of candesartan and other AT(1) receptor blockers to impair angiotensin II-induced AT(1) receptor activation after wash-out
Pharmacological characterization of BR-A-657, a highly potent nonpeptide angiotensin II receptor antagonist
Angiotensin-II mediates nonmuscle myosin II activation and expression and contributes to human keloid disease progression
Cost-effectiveness of candesartan versus losartan in the primary preventive treatment of hypertension
Pharmacokinetic-pharmacodynamic modeling of the antihypertensive effect of eprosartan in Black and White hypertensive patients
On the 'micro'-pharmacodynamic and pharmacokinetic mechanisms that contribute to long-lasting drug action
Comparative effect of candesartan and amlodipine, and effect of switching from valsartan, losartan, telmisartan and olmesartan to candesartan, on early morning hypertension and heart rate
Effect of switching from telmisartan, valsartan, olmesartan, or losartan to candesartan on morning hypertension
Discovery of potent, metabolically stable purine CRF-1 antagonists with differentiated binding kinetic profiles
Radioligand binding to intact cells as a tool for extended drug screening in a representative physiological context
Influence of ligand binding kinetics on functional inhibition of human recombinant serotonin and norepinephrine transporters
The MCH(1) receptor, an anti-obesity target, is allosterically inhibited by 8-methylquinoline derivatives possessing subnanomolar binding and long residence times
On the different experimental manifestations of two-state 'induced-fit' binding of drugs to their cellular targets
Comparative assessment of angiotensin II type 1 receptor blockers in the treatment of acute myocardial infarction: surmountable vs. insurmountable antagonist
The angiotensin II type 1 receptor antagonist Losartan binds and activates bradykinin B2 receptor signaling
AT1 receptor blocker potentiates shear-stress induced nitric oxide production via modulation of eNOS phosphorylation of residues Thr(495) and Ser(1177.)
No substantial gender differences in suspected adverse reactions to ACE inhibitors and ARBs: results from spontaneous reporting system in Campania Region
A Four-Point Screening Method for Assessing Molecular Mechanism of Action (MMOA) Identifies Tideglusib as a Time-Dependent Inhibitor of Trypanosoma brucei GSK3β.
Nifedipine plus candesartan combination increases blood pressure control regardless of race and improves the side effect profile: DISTINCT randomized trial results
Current topics in angiotensin II type 1 receptor research: Focus on inverse agonism, receptor dimerization and biased agonism
International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli [corrected].
In vitro antagonistic properties of a new angiotensin type 1 receptor blocker, azilsartan, in receptor binding and function studies
A systematic comparison of the properties of clinically used angiotensin II type 1 receptor antagonists
Neuroprotective effects of AT1 receptor antagonists after experimental ischemic stroke: what is important?
Is the newest angiotensin-receptor blocker azilsartan medoxomil more efficacious in lowering blood pressure than the older ones? A systematic review and network meta-analysis.
Perspective: Implications of Ligand-Receptor Binding Kinetics for Therapeutic Targeting of G Protein-Coupled Receptors.
Adrenal angiotensin II type 1 receptor biased signaling: The case for "biased" inverse agonism for effective aldosterone suppression.
The Number of Pills, Rather Than the Type of Renin-Angiotensin System Inhibitor, Predicts Ambulatory Blood Pressure Control in Essential Hypertensives on Triple Therapy: A Real-Life Cross-Sectional Study.
Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.