Insights into alpha1 adrenoceptor function in health and disease from transgenic animal studies

Alpha(1)-adrenoceptors (ARs) mediate some of the main actions of the natural catecholamines, epinephrine and norepinephrine, and have a crucial role in the regulation of arterial blood pressure. Since alpha(1)-AR was subdivided into three subtypes (alpha(1A)-AR, alpha(1B)-AR and alpha(1D)-AR), the search has been on to discover subtype-specific physiological roles and to develop subtype-selective agonists and antagonists. Recently, several strains of genetically engineered mice have become available. Studies with these mice have provided several clues to help elucidate subtype-specific physiological functions; for instance, alpha(1A)-AR and alpha(1D)-AR subtypes play an important role in the regulation of blood pressure, suggesting that subtype-selective antagonists might be desirable antihypertensive agents. The ability to study subtype-specific functions in different mouse strains by altering the same alpha(1)-AR in different ways strengthens the conclusions drawn from pharmacological studies. Although these genetic approaches have limitations, they have significantly increased our understanding of the functions of alpha(1)-AR subtypes.