Here we demonstrate that the development of angiogenesis inhibitor-induced hypertension and albuminuria is solely dependent on the ETA receptor and that an upregulation in PGI2 plays a previously unidentified role in the deleterious effects of angiogenesis inhibitors.
These findings highlight the role of endothelin-1 in driving biventricular remodeling secondary to RV hypertension and suggest that early therapy with an endothelin-1 receptor blocker may be beneficial in attenuating biventricular remodeling but that late therapy is also effective.
G<sub>s</sub>-coupled GPCR signalling is regulated by G protein-coupled receptor kinases (GRK) and arrestin proteins, and dysregulation of Gs/GPCR signalling is thought play a role in the development of hypertension, which may be a consequence of enhanced GRK2 and/or arrestin expression.
The present study show that hypertension yet prevail after gastric bypass surgery and the ET(A) receptor antagonist BQ123 may be a useful tool in reducing blood pressure in obese hypertensive patients.
G-protein coupled receptor (GPCR) mediated activation of the MAPK signalling cascade is a key pathway in the induction of hypertrophic remodelling of the heart - a response to pathological cues including hypertension and myocardial infarction.
Furthermore, the DDAH1 and COL18A1 genes were associated with systolic BP change (P < 1.00 × 10(-6) and P = 4.00 × 10(-6), respectively), while EDNRA was associated with hypertension incidence (P = 2.39 × 10(-4)).
These include the contribution of variants of the regulator of G protein signaling (RGS) protein to hypertension; the role variants of the activator of G protein signaling (AGS) proteins to phenotypes (such as the type III AGS8 variant to hypoxia); the contribution of G protein-coupled receptor kinase (GRK) proteins, such as GRK4, in disorders such as hypertension.
Exposure of COX-2 null mice to hypoxia resulted in severe pulmonary hypertension characterized by enhanced pulmonary vascular remodeling and significant up-regulation of the endothelin-1 receptor ET(A)R in the lung after hypoxia.
Systemic hypertension is associated with increased ET-1 and ET(A) receptor mRNA expression, whereas insulin-dependent diabetes down-regulates ET(A) receptor mRNA expression in the internal mammary artery in patients with coronary artery disease undergoing bypass grafting.
In the case of the G protein-coupled receptor kinases (GRKs), identified originally in the retinal tissues that converge on rhodopsin, proteins such as GRK4 have been identified that have been subsequently associated with hypertension.
In addition, an 'uncoupling' of the G-protein-coupled receptor/G-protein complex is the principal mechanism underlying impaired G-protein-coupled-receptor-mediated vasodilatation in hypertension.
In Japanese patients with newly diagnosed, untreated hypertension (n = 184), we studied polymorphisms in 10 genes, including G protein-coupled receptor kinase type 4 (GRK4), some variations of which are associated with hypertension and impair D1 receptor (D1R)-inhibited renal sodium transport.
Further studies are indicated, especially in view of the reported efficacy of endothelin-1 receptor blockers in treating hypoxia-associated pulmonary hypertension.
They also demonstrate that selective blockade of ETA receptors is superior to nonselective ETA/ETB in attenuating hypertension, hypertensive organ damage, and survival rate.
G-protein-coupled receptor kinases (GRKs) are implicated in the pathophysiology of human diseases such as arterial hypertension, heart failure and rheumatoid arthritis.
STRIDE 1: effects of the selective ET(A) receptor antagonist, sitaxsentan sodium, in a patient population with pulmonary arterial hypertension that meets traditional inclusion criteria of previous pulmonary arterial hypertension trials.
Chronic ET(A) receptor blockade normalizes blood pressure, prevents upregulation of vascular ET-1, and improves endothelial dysfunction in 11beta-HSD inhibitor-induced hypertension and may emerge as a novel therapeutic approach in cardiovascular disease associated with reduced 11beta-HSD activity.
These findings demonstrate that endogenous overexpression of preproET-1, accompanied by an elevation of plasma ET-1 concentrations to the levels seen in pathophysiological states, can cause systemic hypertension through the activation of the ETA receptor.