As heart failure (HF) is a devastating health problem worldwide, a better understanding and the development of more effective therapeutic approaches are required. HF is characterized by sympathetic system activation which stimulates α- and β-adrenoceptors (ARs). The exposure of the cardiovascular system to the increased locally released and circulating levels of catecholamines leads to a well-described downregulation and desensitization of β-ARs. However, information on the role of α-AR is limited. We have performed a systematic literature review examining the role of both cardiac and vascular α1-ARs in HF using 5 databases for our search. All three α1-AR subtypes (α1A, α1B and α1D) are expressed in human and animal hearts and blood vessels in a tissue-dependent manner. We summarize the changes observed in HF regarding the density, signaling and responses of α1-ARs. Conflicting findings arise from different studies concerning the influence that HF has on α1-AR expression and function; in contrast to β-ARs there is no consistent evidence for down-regulation or desensitization of cardiac or vascular α1-ARs. Whether α1-ARs are a therapeutic target in HF remains a matter of debate.

The first part of the review presents data on localization of alpha 1-adrenoceptor (AR) in the heart, including plasma and nuclear membranes, on its relative concentrations in the myocardium, on three alpha1-AR (A-, B- and D-) subtypes, the two of which (A and B) are mainly expressed in the human and mouse myocardium and all the three subtypes are expressed in rat\'\'s myocardium. It also reports that the activation of alpha 1-AR induces inotropic effect (positive, negative or biphasic), luzitropic effect, chronotropic effect (the latter can be also positive or negative), and arrhythmogenic effects. The review provides information on the mechanisms forming the basis of these effects, including the role of G q- and G i-proteins, individual isoforms of phospholipase C, phosphatidylinositol 3-kinase, phosphatidylinositol 4,5-biphosphate, diacylglycerol, inositol triphosphate, protein kinase C, protein kinase D, NO-synthase and ion channels. It discusses the literature data on the role of individual subtypes of alpha 1-AR in the implementation of these effects. It reports on the stability of alpha1-AR to desensitization, which is important for the realization by the receptors of their trophic function.

Silodosin is a highly selective α1A-adrenoceptor antagonist indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). Oral silodosin had a rapid onset of effect in men with lower urinary tract symptoms (LUTS) associated with BPH, with improvements seen in voiding and storage symptoms, maximum urinary flow rate and health-related quality of life in well-designed, 12-week trials. Silodosin was noninferior to tamsulosin in terms of improving LUTS associated with BPH. The efficacy of silodosin was maintained in 9-month extension studies and was also seen in a phase IV study conducted in a real-world setting. Silodosin was generally well tolerated and was associated with a low risk of orthostatic hypotension. Abnormal ejaculation was the most commonly reported adverse event, although few patients discontinued treatment with silodosin because of this adverse event. In conclusion, silodosin is a useful option for the treatment of LUTS associated with BPH.

Intraoperative floppy-iris syndrome (IFIS) is associated with the use of systemic alpha(1)-antagonists, and tamsulosin in particular. The incidence and severity of IFIS are variable; however, the syndrome is associated with a higher rate of cataract surgical complications, especially when the condition is not recognized or anticipated. Questioning cataract patients preoperatively about current or previous use of alpha(1)-antagonists is therefore important. Intraoperative floppy-iris syndrome surgical management strategies include pharmacologic measures, the use of high-viscosity ophthalmic viscosurgical devices, and mechanical dilating devices. However, sphincterotomies and pupil stretching are ineffective. Whether used alone or in combination, these small-pupil techniques improve the surgical success rate in these cases. Stopping the alpha(1)-antagonist preoperatively is of questionable value.

Two phase III studies with tamsulosin, a selective alpha1A-adrenergic receptor antagonist, were conducted to evaluate the safety and efficacy of the standard treatment doses of 0.4 mg/day and 0.8 mg/day in patients with symptoms of benign prostatic hyperplasia (BPH). These large-scale clinical trials were the first to include extensive testing for possible drug-induced orthostatic hypotension (OH). The frequency of positive orthostatic tests and magnitude of vital sign changes were compared among tamsulosin and placebo-treated groups. The results indicate that tamsulosin up to 0.8 mg/day does not induce higher risk of OH than that of placebo. Data from post-marketing surveillance (PMS) studies of tamsulosin indicate that the incidence of hypotension and syncope is extremely low in community-dwelling elderly men treated for BPH. From the results of the phase III studies, PMS studies and an active-controlled clinical pharmacology study, we conclude that the orthostatic test is a useful and convenient method to evaluate the risk of OH and syncope during the investigational stage.